Aav native-neuro platform and use for neuronal disease gene therapy

ABSTRACT

The invention described herein provides methods and compositions for using recombinant AAV-based viral vectors to express any gene-of-interest (GOI) under its native promoter and a proprietary heterologous enhancer, preferably expressing a GOI defective in a neuronal disease or disorder in order to treat the neuronal disease or disorder.

RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No. 63/014,283, filed on Apr. 23, 2020, the entire contents of which is expressly incorporated herein by reference.

BACKGROUND OF THE INVENTION

Gene-based neurotherapeutics holds great therapeutic potential. Clinical efficacy has already been obtained for central nervous system (CNS) diseases and eye disease through Adeno Associated Virus (AAV) gene therapy. The general lack of current effective neurotherapies for many devastating neurologic diseases portends great future demands for AAV gene-based neurotherapy.

Efficient and specific delivery to a target organ, such as the brain, is a rate limiting step in many protein-based therapeutics. There are multiple barriers to efficient direct protein delivery to the CNS.

One of the great challenges lies in the blood-brain barrier (BBB). Unlike the vasculature in other organ systems, the brain endothelium forms intercellular tight junctions (TJs) that limit greatly the paracellular access of blood-borne components to the tissue parenchyma. As a consequence of this “physical barrier” generated by TJs, gene transfer vehicles attempting entry into the CNS are forced to go through the transcellular route. There, however, specialized lumen facing efflux transporters, which include both the ABC family of transporters and multidrug resistance-related proteins, contribute to the formation of the “transport barrier” that prevents xenobiotic substances from gaining access to the neuronal environment. Another obstacle that partially prevents endothelial crossing of gene-therapy vehicles is the trancytotic/endosomal sorting, which can lead to degradation. Although the endothelium is the greatest obstacle in restricting access to the CNS, the presence of a complex extracellular space, molecular composition and geometry also significantly impede diffusion of viral-based gene delivery systems. That is, even if a therapy can be designed to target one of these receptors and traverse the BMVEC cytoplasm to be released at the basal cell membrane, only the first of many guardian mechanisms at the BBB has been overcome. If neurons are the target cell type, once the BBB endothelium has been passed, the basal lamina, pericytes, microglial ramifications, and the glial limitans comprised of astrocytic endfeet still have to be navigated before surpassing all of the checkpoints at the BBB and encountering a neuron.

As a result, intravascular administration of most viral vectors with the exception of few AAV serotypes has proven unsuccessful in the treatment of neurological diseases, potentially because these gene delivery platforms cannot negotiate their way across the BBB to access their target cells.

Another challenge lies in the promoters used in the gene therapy vectors. With the discovery of new viral vectors, mainly AAV capsids, with remarkable CNS tropism after vascular, CSF administration, or direct intracranial injection, the field of AAV mediated CNS gene therapy is accelerating rapidly towards clinical trials in a number of neurological diseases, and the expedient approach has been to use specific promoters with a proven track record of mediating long-term gene expression given the serious nature of many of these diseases, many of which are pediatric.

The majority of the pre-clinical studies have used strong ubiquitous promoters to provide a broad overview of transgene expression in different tissues and cell types throughout the body after intravascular infusions, or CNS cell types after intracranial delivery.

The CAG/CBA/CB promoter is generally viewed as a ubiquitous promoter as it works in numerous tissues and cell types. However, the assumption that it is highly active in every cell type may not be entirely warranted in the CNS. Studies have been conducted using AAV vectors with the same capsid but carrying different CNS cell specific promoters or the CBA promoter. The apparent discrepancy in CNS transduction profiles of these different AAV vectors suggests that the CBA promoter may not mediate detectable transgene expression in all cell types in the brain. Additional experiments have been conducted using AAV vectors with numerous tropism carrying the cytomegalovirus (CMV), CBA, Rous sarcoma virus (RSV), or human GUSB promoters to drive transgene expression, in the context of intra-parenchymal delivery to different brain structures.

In clinical studies, the majority of AAV vectors for treating neurological diseases have used the CMV immediate early promoter followed by a chimeric intron composed of a CMV splice donor and a human globin splice acceptor, or a version of the CAG/CBA promoter (supra). Two other clinical trials have tested AAV vectors carrying mammalian promoters such as the mouse phosphoglycerate kinase (PGK) promoter, or the rat neuron-specific enolase (NSE) promoter. The choice of promoters is based on the availability of extensive data from pre-clinical studies in different animal models showing that AAV-mediated transgene expression under these promoters is stable and long lasting in the mammalian brain. The stability of AAV gene expression in the human brain has been evaluated in clinical trials using an AAV2 vector encoding aromatic amino acid decarboxylase (AADC) injected into the putamen of Parkinson's disease patients, or children afflicted with AADC deficiency.

An indisputable fact about these AAV-CMV or AAV-CAG/CBA vectors is their ability to drive strong gene expression in many neurons in the CNS of multiple species. The disparate CNS transduction results between cellular promoters and strong non-mammalian promoters raises the possibility that the current generation of AAV vectors express transgenes at exceptionally high levels in a small percentage of all cells that harbor transcriptionally ready vector genomes in the nucleus. A recent report documented considerable toxicity in non-human primates (NHPs) receiving intraparenchymal injections of an AAV2 vector encoding human acid sphingomyelinase. Another safety study on intracranial delivery of an AAVrh10 vector encoding human tripeptidyl peptidase (TPP-I) in NHPs reported white matter edema and inflammation. The interpretation of these results is complicated, but a possible interpretation of the results is that these inflammatory responses are secondary to protein expression overload and non-specific expression in AAV transduced neurons.

The potential for toxicity due to excessive transgene expression is particularly acute in neurological diseases where the expressed proteins are not secreted, and thus the need for high level expression is even less. In one particular case, the development of an AAV gene therapy approach for Rett syndrome represents a significant challenge to the prevalent approach of simply using strong promoters. This disease is caused by mutations in the MeCP2 gene on the X-chromosome. Interestingly, duplication of this gene also leads to neurodevelopmental delays, suggesting that expression of this gene in the CNS need to be tightly controlled, which is a challenge to current AAV gene therapy.

SUMMARY OF THE INVENTION

The invention described herein provides a gene replacement therapy platform to replace mutated genes by AAV Gene Therapy.

According to the invention described herein, about 40 exemplary central nervous system (CNS) disease drug protypes are packaged in recombinant AAV vectors for intravenous administration to a patient, in order to express functional genes in native neuronal cells. The technology is designed for intravenous dosing of AAV to express genes precisely in intended cell types by using endogenous/native promoter fused with viral/heterologous enhancer.

In an exemplary embodiment, the gene cassette in the AAV vector of the invention begins with AAV inverted terminal repeat (ITR), followed by proprietary heterologous enhancer, followed by a native promoter of a gene of interest (GOI), 5′UTR, proprietary codon optimized gene of interest (GOI), 3′UTR, and ends in another AAV inverted terminal repeat (ITR).

Thus one aspect of the invention provides a recombinant adeno-associated viral (rAAV) vector, comprising: (1) a polynucleotide comprising a gene of interest (GOI), under the transcriptional control of the native/endogenous promoter of said GOI; (2) a heterologous enhancer that enhances transcription of the GOI from the native/endogenous promoter; and, (3) a pair of inverted terminal repeat (ITR) flanking the polynucleotide.

In certain embodiments, the GOI is a neuronal gene, or is a gene expressed in neuronal tissues (CNS and/or PNS).

In certain embodiments, the GOI is defective (e.g., loss-of-function) in a neuronal disease or condition.

In certain embodiments, the neuronal disease or condition is a CNS disease or condition.

In certain embodiments, the CNS disease or condition is: Ceroid-Lipofuscinosis, Fucosidosis, Giant Axonal Neuropathy, Globoid cell leukodystrophy, Mucolipidiosis Type IV, Neuronal Ceroid Lipofusinoses, Niemann-Pick Disease, Sandhoff Disease, Sanfilippo syndrome, Tay-Sachs Disease, Hunter Syndrome, Sialidosis, Multiple Sulfatase Deficiency, Childhood Epilepsy, CMT Peripheral Neuropathy, Neuronal Ceroid Lipofusinoses, Aspartylglycosaminuria, Mucopolysaccharidoses, Parkinsons Disease/Symptoms, GM1-Gangliosidosis, Charcot-Marie-Tooth Type 1A, Retts Syndrome, Dannon Disease, Mucopolysaccharidoses (due to GNS, HGSNAT, NAGLU, or ARSB), Sly Syndrome, Biotin basal ganglia disease, Pelizaeus-Merzbacher disease, Neuronal Ceroid Lipofusinoses, Canavan Disease, Beta-Mannosidosis, Wolman Disease, Cystinosis, Alzheimer's Disease/Symptom, Salla Disease, Jansky-Bielschowsky disease, Neuronal ceroid lipofuscinoses, or GM2 gangliosidosis.

In certain embodiments, the GOI is: CLN3, FUCA1, GAN, GALC, MCOLN1, PPT1, SMPD1, HEXB, SGSH, HEXA, IDS, NEU1, SUMF1, GAT1/SLCA1, FIG. 4 , CLN5, AGA, IDUA, GDNF, GLB1, PMP22/MFN2, MECP2, LAMP2, NAGLU, ARSB, GUSB, SLC19A3, PLP1, TPP1/CLN2, ACY2/ASPA, MANBA, LIPA, CTNS, GNS, HGSNAT, NEUROD1, SLC17A5, CLN6, CLN8, or GM2A.

In certain embodiments, the rAAV has a tropism for neuronal cells, or for a cell in neuronal tissue.

In certain embodiments, the rAAV is AAV9, AAV2.5, rAAVrh.39, rAAVrh.43, rAAV7, rAAVrh.8 or rAAVrh.10, preferably AAV9.

In certain embodiments, the rAAV comprises AAV9, AAV2.5, rAAVrh.39, rAAVrh.43, rAAV7, rAAVrh.8 and rAAVrh.10 capsids, preferably AAV9 capsids.

In certain embodiments, the polynucleotide further comprises a 5′-UTR coding region, and a 3′-UTR coding region.

In certain embodiments, the heterologous enhancer is a viral enhancer.

In certain embodiments, the viral enhancer is CMV enhancer.

In certain embodiments, the viral enhancer is SV-40 enhancer.

In certain embodiments, the heterologous enhancer comprises a polynucleotide of SEQ ID NO: 1.

Another aspect of the invention provides a pharmaceutical composition comprising any one of the rAAV vector of the invention.

In certain embodiments, the pharmaceutical composition is formulated for intravenous administration (e.g., to the blood) or intrathecal administration (e.g., to spinal fluid).

Another aspect of the invention provides a cell infected with any one of the rAAV vector of the invention.

Another aspect of the invention provides a recombinant AAV virus comprising any one of the rAAV vector of the invention, wherein the serotype or pseudotype of the recombinant AAV virus is for preferential infection of a neuronal cell or a cell in neuronal tissue.

Another aspect of the invention provides a method of treating a (genetic) disease or disorder in a subject, the method comprising administering the recombinant AAV virus of the invention into the subject.

In certain embodiments, the genetic disease or disorder is a neuronal disease or disorder, and/or wherein the recombinant AAV virus preferentially infects a neuronal cell or a cell in neuronal tissue of the subject, thereby treating the neuronal disease or disorder.

In certain embodiments, the rAAV virus is administered to the subject intravenously or intrathecally.

Another aspect of the invention provides a method of producing any one of the rAAV vector of the invention, the method comprising introducing any one of the rAAV vector of the invention into a packaging cell line that constitutively or inducibly provides rep/cap proteins in trans.

In certain embodiments, the rep/cap proteins comprise one or more AAV9 capsid proteins.

It should be understood that any one embodiment of any one of the aspects of the invention above, including specific embodiments described only in one section of the application, can be combined with one or more additional embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic drawing (not to scale) showing a generic structure of the subject rAAV vector, as well as an intended mode of action for the vector. The Gene of Interest (GOI) is put under the control of its native promoter. Transcription from the native promoter is further enhanced by the presence of a powerful enhancer, such as a viral enhancer like CMV enhancer, to facilitate the expression of the GOI in the native cells such GOI is normally expressed. The entire recombinant sequence is flanked by two AAV ITR sequences, such as AAV9 ITR sequences for the preferred neuronal cell tropism.

FIG. 2 is a gel image confirming the construction of rAAV viral vectors comprising a number of representative GOI's that are defective in neuronal diseases/disorders. Also shown is a rAAV vector encoding a GFP reporter gene, which can be switched out by any of the GOI's.

FIG. 3 is a gel image confirming the construction of additional rAAV viral vectors comprising a number of representative GOI' s that are defective in neuronal diseases/disorders.

DETAILED DESCRIPTION OF THE INVENTION 1. Overview

The invention described herein provides methods and compositions for using recombinant viral vectors, such as AAV-based viral vectors or lentiviral vectors to express any gene-of-interest (GOI) under the control of its native promoter so that the GOI is preferentially and exclusively expressed in the cells the GOI is intended to be expressed. The GOI is further under the transcriptional control of a powerful heterologous enhancer, such as a viral enhancer like CMV enhancer, which further boosts the transcription and expression of the GOI. Therefore, after a single intravenous treatment, the protein product of interest is expressed at high levels only in the endogenous/native cell types, thereby improving therapeutic safety and efficacy.

Thus in one aspect, the invention described herein provides a recombinant adeno-associated viral (rAAV) vector, comprising: (1) a polynucleotide comprising a gene of interest (GOI), under the control of the native/endogenous promoter of said GOI; (2) a heterologous enhancer that enhances transcription of the GOI from the native/endogenous promoter; and, (3) a pair of inverted terminal repeat (ITR) flanking the polynucleotide.

In certain embodiments, the GOI is a neuronal gene.

In certain embodiments, the neuronal gene is defective (e.g., loss-of-function) in a neuronal disease or condition.

In certain embodiments, the neuronal disease or condition is a CNS disease or condition.

In certain embodiments, the CNS disease or condition is: Ceroid-Lipofuscinosis, Fucosidosis, Giant Axonal Neuropathy, Globoid cell leukodystrophy, Mucolipidiosis Type IV, Neuronal Ceroid Lipofusinoses, Niemann-Pick Disease, Sandhoff Disease, Sanfilippo syndrome, Tay-Sachs Disease, Hunter Syndrome, Sialidosis, Multiple Sulfatase Deficiency, Childhood Epilepsy, CMT Peripheral Neuropathy, Neuronal Ceroid Lipofusinoses, Aspartylglycosaminuria, Mucopolysaccharidoses, Parkinsons Disease/Symptoms, GM1-Gangliosidosis, Charcot-Marie-Tooth Type 1A, Retts Syndrome, Dannon Disease, Mucopolysaccharidoses (due to GNS, HGSNAT, NAGLU, or ARSB), Sly Syndrome, Biotin basal ganglia disease, Pelizaeus-Merzbacher disease, Neuronal Ceroid Lipofusinoses, Canavan Disease, Beta-Mannosidosis, Wolman Disease, Cystinosis, Alzheimer's Disease/Symptom, Salla Disease, Jansky-Bielschowsky disease, Neuronal ceroid lipofuscinoses, or GM2 gangliosidosis.

In certain embodiments, the GOI is: CLN3, FUCA1, GAN, GALC, MCOLN1, PPT1, SMPD1, HEXB, SGSH, HEXA, IDS, NEU1, SUMF1, GAT1/SLCA1, FIG. 4 , CLN5, AGA, IDUA, GDNF, GLB1, PMP22/MFN2, MECP2, LAMP2, NAGLU, ARSB, GUSB, SLC19A3, PLP1, TPP1/CLN2, ACY2/ASPA, MANBA, LIPA, CTNS, GNS, HGSNAT, NEUROD1, SLC17A5, CLN6, CLN8, or GM2A.

In certain embodiments, the rAAV has a tropism for neuronal cells. In certain embodiment, the rAAV serotype is, AAV2.5, rAAVrh.39, rAAVrh.43, rAAV7, rAAVrh.8 or rAAVrh.10.

In certain embodiments, the rAAV serotype is AAV9. In certain embodiments, the rAAV has a pseudotype of xxx. In certain embodiments, the polynucleotide further comprises a 5′-UTR coding region, and a 3′-UTR coding region.

In certain embodiments, the heterologous enhancer is a viral enhancer.

In certain embodiments, the viral enhancer is CMV enhancer.

In certain embodiments, the viral enhancer is SV40 enhancer.

Another aspect of the invention provides a pharmaceutical composition comprising the rAAV vector of the invention.

In certain embodiments, the pharmaceutical composition is formulated for intravenous administration.

Another aspect of the invention provides a cell infected with the rAAV vector of the invention.

Another aspect of the invention provides a recombinant AAV virus comprising the rAAV vector of the invention, wherein the serotype or pseudotype of the recombinant AAV virus is for preferential infection of a neuronal cell.

Another aspect of the invention provides a method of treating a (genetic) disease or disorder in a subject, the method comprising introducing the recombinant AAV virus of the invention into the subject.

In certain embodiments, the genetic disease or disorder is a neuronal disease or disorder, the recombinant AAV virus preferentially infects a neuronal cell of the subject, and treats the neuronal disease or disorder.

Another aspect of the invention provides a method of producing the rAAV vector of the invention, comprising introducing the rAAV vector of the invention into a packaging cell line that constitutively or inducibly provides rep/cap proteins in trans.

With the general aspects of the invention described, further detailed embodiments of the invention are provided below.

2. Treatable Disease or Conditions

The recombinant AAV vector and recombinant AAV virus of the invention, together with the pharmaceutical composition comprising the same, can be used to treat a number of diseases and conditions, particularly neuronal diseases or indications treatable by gene therapy.

Diseases or conditions treatable by the AAV vector/virus/method of the invention are typically characterized by lacking a functional neuronal protein or enzyme, which neuronal diseases or indications can be alleviated (if not cured), treated, or prevented (e.g., at least the onset is delayed), by providing functional versions of the proteins or enzymes. The externally provided functional versions of the proteins or enzymes may be identical in sequence to the wild-type proteins or enzymes that are lacking in a host having such diseases or conditions, or may be a variant of the wild-type proteins or enzymes.

In certain embodiments, the neuronal diseases or conditions can be treated by introducing into the host the subject AAV virus that will infect target host (neuronal) tissues, and stably express the encoded GOI that is defective in the diseases or conditions throughout the life span of the host. The subject AAV virus may only need to be introduced into the host once, or can be introduced into the host multiple times as needed.

A few representative polynucleotide sequences of the invention encoding several genes-of-interest (GOI) are listed below. These polynucleotide sequences can be part of the subject AAV vector sequences. These sequences are for illustrative purpose only and are non-limiting.

Giant Axonal Neuropathy (GAN)

Giant axonal neuropathy (GAN) is a severe, slowly progressive neurodegenerative disorder characterized by progressive motor and sensory peripheral neuropathy, central nervous system involvement (including pyramidal and cerebellar signs), and characteristic kinky hair in most cases. GAN is inherited as an autosomal recessive trait, and is associated with more than 50 different causative mutations in GAN gene (16q24.1), encoding the ubiquitously expressed cytoskeletal protein gigaxonin.

Disease prognosis varies but is usually poor. Most patients become wheelchair-dependent in the second decade of life, and eventually progress to a bedridden state in early adulthood. Secondary complications, such as respiratory failure, may occur. Life expectancy does not exceed the third decade.

Current GAN treatment is symptomatic, focusing on stimulating intellectual and physical development, as well as communication skills, through physical, occupational and speech therapy, starting from the initiation of symptoms. Skeletal deformities and ophthalmoplegia may need surgery.

Thus in one embodiment, the GOI is GAN that encodes gigaxonin, and the disease or condition treatable by the subject AAV vector/virus is Giant Axonal Neuropathy (GAN). The composition and methods of the invention can be used to produce gigaxonin expressed permanently from AAV vectors stably maintained with the host's genome as extra chromosomal material, in native neuronal cells that normally express GAN, thus effectively treating giant axonal neuropathy.

A representative polynucleotide of the invention that can be encoded by the AAV vector of the invention is described below.

(SEQ ID NO: 2) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC AATAATGACGTATGTTCCCATAGTAACGCCAATAG GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA TCATATGCCAAGTACGCCCCCTATTGACGTCAATG ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT CTACGTATTAGTCATCGCTATTACCATG CTCACAGGGATACTGGGTAGGTATCATGGAGAAGA TAAGTCCAAGCTGCTTGTCTTGTGTGTTTCTTACC TTTTTAAATATATTTTTCGGCCGGGTGTGGTGGCT TATGCCTGTAATTCCAGTACTTTGGGAAGCCAAGG TGGGCGGATCACAAGGTCAGGAGTTCGATACCAGC CTGGCCAACATGGTAAAACCCCATCTCTACTAAAG ATGCAAAAGTTAGCCAGGCATGGTGGCACATGCCT GTAGTCCCAGCTACTTGGGAGGCTGAGGCAGGAGA ACCACTTGAACCCGGGAGGCGGAGGTTGCAGTGAA CAGAGATTGCACAACTGCACTCCAGCCTGGGCAAT AGAGGGAGACTCCATCTCAAAAAAAAAAAAGAAAG AAGAAAATATTTTTCAACATCCACAAAAATATAGA AACAGTACAATGAATCTCCACATCCCCATTAAACA TCCACAACAATATAGAGACAGTACAACGAATCTCC ACATCCCCATTACGTGGCTTTAACAATTAGTAACT TGCGGCCACTTTTGACTCATCTACACTCCCATCTG CTTCCCCATCCCTTTGTTTTGTTTTGAAGCAAATC CTAGACATCTTTATCATTGCATCCGGGAACACTGA GCTGCATTTACAGAAGAAAGTGGAAATGCATGTGT CTTCCACAGCCGTACCCTCCCCATCTATTCTGCCC TGAAAACAGTTAGATACTCGGATTCCTGCCAGTGA CTCCAAAGCCTTGGCTGGTTCAGGGTAAATACCCA AGACTTTATTGGAGCCTTTCAGTTGGTTGAAGGAC AGTGAAAATTCCATCCTGTCTTGCCTGGAATGCTA GCCACATTCTTCTGGTCCGGAGTCCTCATACAATT GCTAATTTTTTAGAGGCTTATGGAGTCCCTAACGT TTGCACAAAATGGTTGCTACATTCCACACTCCCAT GTGCCCTGAGCAACCTCCAGGGAAACTTCAGATAC CGTGGGGCTTGGCCTGCCAGCTGAGCTGACCCAGC GATCCTTTCTATCACAGCTTTGATCTTCACTGGGT TGGGAGCCTGTCTGAATCTAAACATCTGCCTCTCT ACTGCCCACCCCTTCAGCATTTCCTAGCTCTCCCT GAAAGGTGCAAACATGCATGCAGTTACTCAAACAG AATATTTATCCTTAACTCCCTCTCCCTCACAATTT CTTTTAAAACAATCCACTATTGTCTACCCCCGCCC CCGCATCACCCTTTCATCCAGGTGCCCATTCCCTT CTCTCTAGTCCTGCAATACCTAAGCATCGATCTGC CTTTAGCACATCCATCCCCGCCTTATTCTCCACGC AGGAGCTGAGTGACCTGCACAAAATCCCCTGCTAA ATACGGTACTTCCATGGTTCTTCACCACTGCAGAA ACCAAACTCCTTCCCACACCAAGGAGGCCCTGCAA AATTTAAGGCCTCCTTCGGACTTCTCCAGCTTCAT CTGCTACATCTCCTTCCTAGCCCGCAACCAAAACC ATCTTTTCCGGGTCTGTTTTCTCGGGTTTTTGTCC TCTCACCTGGGCAGCTCCTTTTCTCTCATAAATAA AGAAAGCTACAGCGACTTCGCCCTTGCTTCCATGC ATCATCTCATGAGTCCACAACAACACTAAGAATTC GCTTTCATTTTGCAGACGGAGAAACTGAGGATGGG CACCTTACCCATGGCCACAGAGCTAGTAAGTGGAA CAGCTGCAACCAGGATTCAAACTCGCGGCTCCAGA GGCCACAGGCTTAACCACGGAATCCTAGCCCGCCC GCACATCCCTCCATCGCGGGAGCGACCTATCTCAT CCGTAGACACCTTCCGCTGCACCCAGCCGCAGCTG GTCAGGCGGGCGGAGGAAGGAGGCTTCTGATTGGC CATCTCCAGCAGCGGAGGCGAGAAGGCGGGGAGCG ACGGTGCGGGGGCGTCGCGGAGAAATGACTTCATG ACGCGGCTTCTTAAAGGCGCCGGCCCAGCGCGCCG CGGA

ATGGCTGAGGGAAGTGCGGTCTCAGACCCCCAACA CGCTGCAAGACTTCTGCGAGCTCTCTCATCTTTCA GAGAGGAGTCACGCTTCTGTGACGCACACTTGGTC CTTGACGGAGAAGAGATACCTGTCCAGAAAAATAT ACTTGCCGCTGCATCCCCATACATTCGCACCAAGC TGAACTACAATCCCCCTAAAGACGACGGGAGCACC TATAAAATCGAATTGGAGGGCATCTCCGTGATGGT AATGCGAGAGATACTGGATTACATATTTAGCGGCC AGATCAGGCTGAATGAGGATACGATCCAAGATGTT GTACAGGCAGCGGACTTGCTGCTTCTGACGGACCT TAAGACCCTTTGCTGCGAGTTCCTCGAAGGGTGTA TTGCTGCCGAGAATTGTATCGGAATACGAGACTTC GCACTCCATTACTGCCTTCACCACGTTCATTACCT TGCGACAGAGTATTTGGAAACACATTTCCGCGACG TTAGCTCTACAGAGGAATTTCTCGAACTTAGTCCT CAAAAGCTCAAGGAGGTTATTAGTCTTGAAAAGCT CAACGTCGGAAATGAGCGGTACGTGTTTGAGGCCG TGATACGGTGGATCGCCCACGACACCGAGATCCGC AAGGTCCACATGAAGGATGTAATGTCAGCGCTGTG GGTATCCGGTCTTGACTCTTCATACTTGAGAGAGC AGATGCTCAACGAACCTTTGGTGAGGGAAATAGTG AAGGAGTGTAGTAACATCCCCCTCAGCCAACCCCA GCAAGGCGAAGCGATGCTCGCGAACTTCAAGCCCC GAGGCTACAGCGAATGCATAGTAACAGTGGGAGGT GAAGAACGGGTCTCCCGGAAACCCACTGCGGCGAT GCGGTGTATGTGTCCCCTGTATGATCCCAATCGCC AACTTTGGATCGAGCTGGCGCCGCTGTCTATGCCA CGAATAAATCACGGGGTTCTTTCAGCCGAGGGGTT TCTGTTCGTCTTTGGAGGGCAGGATGAGAACAAAC AAACACTCTCCAGTGGGGAGAAATACGACCCCGAT GCAAACACTTGGACAGCTCTGCCACCGATGAACGA AGCCCGACACAACTTTGGTATAGTCGAAATCGACG GTATGCTGTATATCCTTGGAGGAGAGGACGGAGAA AAAGAACTCATCTCCATGGAATGTTACGACATTTA CAGCAAAACTTGGACAAAGCAACCCGACCTTACTA TGGTGAGGAAGATAGGATGTTATGCGGCAATGAAG AAAAAGATATACGCCATGGGAGGCGGTTCTTATGG TAAGCTCTTCGAGAGTGTGGAGTGTTATGACCCTC GAACGCAGCAATGGACAGCCATATGTCCCCTGAAG GAACGGCGATTTGGGGCGGTAGCGTGTGGAGTTGC AATGGAGTTGTACGTTTTCGGAGGTGTTCGAAGTC GGGAGGACGCGCAAGGGTCAGAGATGGTCACATGT AAAAGCGAATTTTATCATGACGAATTTAAGCGGTG GATTTATCTGAACGACCAAAACCTCTGTATTCCAG CTTCCAGTTCCTTCGTATACGGCGCTGTGCCAATA GGTGCGTCAATTTACGTCATAGGCGACTTGGACAC TGGTACTAATTATGATTACGTACGCGAGTTTAAGA GGAGTACAGGCACCTGGCACCACACAAAACCGCTG CTCCCGTCCGATCTGCGAAGGACAGGTTGCGCTGC ATTGAGGATTGCTAACTGCAAACTTTTCCGCCTGC AACTTCAGCAAGGGCTTTTCCGCATACGAGTCCAC AGTCCTGACTATAAAGATGACGACGACAAATA

In the sequence herein, double underlined sequences represent proprietary viral enhancer sequences (SEQ ID NO: 1, see below); bold sequences are native promoter sequences for GAN; italic sequences are coding sequence for the GOI (GAN in this case); the subscripted sequences immediately 5′ and 3′ to the GOI coding sequence are 5′-UTR and 3′-UTR sequences, respectively.

The proprietary enhancer sequences (SEQ ID NO: 1) is listed below.

(SEQ ID NO: 1) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGT ACCTTCTGAGGCGGAAAGAACCAGCGTTACATAACTTACGGTAAATGGCC CGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAATGACG TATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGT GGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATA TGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGG CATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACAT CTACGTATTAGTCATCGCTATTACCATG 

The GAN protein sequence is:

(SEQ ID NO: 3) MAEGSAVSDPQHAARLLRALSSFREESRFCDAHLVLDGEEIPVQKNILAA ASPYIRTKLNYNPPKDDGSTYKIELEGISVMVMREILDYIFSGQIRLNED TIQDVVQAADLLLLTDLKTLCCEFLEGCIAAENCIGIRDFALHYCLHHVH YLATEYLETHFRDVSSTEEFLELSPQKLKEVISLEKLNVGNERYVFEAVI RWIAHDTEIRKVHMKDVMSALWVSGLDSSYLREQMLNEPLVREIVKECSN IPLSQPQQGEAMLANFKPRGYSECIVTVGGEERVSRKPTAAMRCMCPLYD PNRQLWIELAPLSMPRINHGVLSAEGFLFVFGGQDENKQTLSSGEKYDPD ANTWTALPPMNEARHNFGIVEIDGMLYILGGEDGEKELISMECYDIYSKT WTKQPDLTMVRKIGCYAAMKKKIYAMGGGSYGKLFESVECYDPRTQQWTA ICPLKERRFGAVACGVAMELYVFGGVRSREDAQGSEMVTCKSEFYHDEFK RWIYLNDQNLCIPASSSFVYGAVPIGASIYVIGDLDTGTNYDYVREFKRS TGTWHHTKPLLPSDLRRTGCAALRIANCKLFRLQLQQGLFRIRVHSPDYK  DDDDK

Conservative changes to the protein sequence above (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 conservative residue changes, or up to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% conservative residue changes) that result in a functional equivalent version of the protein (e.g., that retains at least 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99% of the wild-type enzyme activity) are also within the scope of the invention.

Likewise, in any of the nucleotide sequence encoding the protein and variants thereof, such as in SEQ ID NO: 2, nucleotide sequence changes that do not result in sequence change of the encoded protein in SEQ ID NO: 3 due to, for example, codon degeneracy, are within the scope of the invention. Further, codon optimization of any of the polynucleotide sequence for optimal expression in a specific type of host cell is also within the scope of the invention (see further details below).

Juvenile Neuronal Ceroid Lipofuscinosis (JNCL or Batten Disease)

Neuronal ceroid lipofuscinosis refers to a family of at least eight genetically separate neurodegenerative lysosomal storage diseases that result from excessive accumulation of lipopigments (lipofuscin) made up of fats and proteins in the body's tissues. The most commonly identified mutations are in the CLN3 gene, located on the short arm of chromosome 16 (16p12.1), found in childhood or juvenile NCLs (JNCLs).

JNCL is an autosomal recessive disorder. The normal function of CLN3 gene is not presently known, but it is known to be a transmembrane protein. Studies of the yeast CLN3 ortholog which encodes Battenin have suggested that the protein may play a role in lysosomal pH homeostasis. Furthermore, recent studies have also implied the protein's role in cathepsin D deficiency; the overexpression of the defective protein appears to have significant effects on cathepsin D processing, with implications suggesting that accumulation of ATP synthase subunit C would result.

All mutations resulting in JNCL have been shown to occur at the CLN3 gene. Of the mutations known to cause JNCL, 85% result from a 1.02 kb deletion, with a loss of amino acids 154-438, while the remaining 15% appear to result from either point or frameshift mutations.

Thus in one embodiment, the GOI is CLN3, and the disease or condition treatable by the subject AAV vector/virus is JNCL. The composition and methods of the invention can be used to produce CLN3 gene product expressed permanently from AAV vectors stably maintained with the host's genome as extra chromosomal material, in native neuronal cells that normally express CLN3, thus effectively treating JNCL.

A representative polynucleotide of the invention that can be encoded by the AAV vector of the invention is described below. Specifically, the proprietary enhancer sequence is in SEQ ID NO: 1. Native CLN3 promoter is known in the art. The coding sequence for CLN3 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

CLN3-DNA

(SEQ ID NO: 4) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC AATAATGACGTATGTTCCCATAGTAACGCCAATAG GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA TCATATGCCAAGTACGCCCCCTATTGACGTCAATG ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT CTACGTATTAGTCATCGCTATTACCATG TTCCCCCAGGGGCGGAAGGGGCCGGATTGGTGGCT CTGGGGTGCATCCCCTCACCTATGATTAGGCTTGC AAAAAAGAACTTGGCTAAACTTTATATTGTGGATA TCTGTGTCTGCCTCCCACCTTCCTGTGACTTCCTT GATGGCAGATGCCATGTATGAAACGCTGCTGAATT TCTAGAGCCCTGCACGTTAGTAGGATTCCATTTTC CATCAGCTGAGTGACCTGGGAGGCACACTAGAGAG GGCACATTTCTTTTCTTTTCTTTTCTTTTTTTTTT TGAGACAGTCTCACTCTGTCACCCAGGCTGGAGTG TAGTGGCGCAGTCTCAGCTCACTGCAACCTCTGCC TCCTGGGTTCAAGTGATTCTCCTGCCTCAGCCTCC CGAGTAGCTGGGATTACAGGTGCGTGCCACCACAC CTGGTTAATTTTTGTATCTTTAGTAGAGACAGGGT TTCACCATGTTAGCCAGGCTGGTTTCGAACTCCTG ACCTCAGGTGATCTGCCCACCTTGGCCTCCCAAAG TGCTGGGATGACAGGCATGAGCCACCACACCCAGA CGAGAGGGCACATTTCCAACTGCATTCTGAAGGCC TGGTGGTGAGAAAGAGCATATAGAGGTGGCACAGC CCATAGCAGAGATGAGGCCAAGGACAAGAAGAGAA TGCAGGATGCCGCTTTCCACCTAGAAGAAGGTAAG GGTATGATTCCTTATTTGGAACTACATAAAGTGAC CTTGCTCTACTTCTCTTCCCCATACCCTCCTTCTC CCCTCCCCAGCCCCACTTTCCTATTCCAATTAGGG CAATTCTATGAAATCACAGCATCAGAATCTTAGGC CTTAAAATCATTTAGTCTGGCCAGGTGCAGTGGCT CACGCCTGTAGTCCTAGCACTTTGGGAAGCCAAGG CAGGTGGATTGCTTGAGCTCAGGAGTTTGAGGCCA CCCTGGGCAACGTGGCAAAATCCAGTCTCTACAAA AAACACAAAAATTAGCTGGGCACAGTGGTGCGCAC CTGCTGTCCCAGCTACTCGGGAGGCTGAGGTGGGA GGATCACCTGAGCCTGGGAGGTCAAGGTTGCAGCA AACCAAGATCCTGCCACTGCACTCCAGCCTGGGCA ACAGAGCAAAACCCTGTCAAAAAAAAAAAAAAAAT CTGGTCTAAGCACCACCTTTGATGGAGGCAGGAAT CCTGCAGCAGCCTGGAGCCAACCCAATGGCTCCCT GCCTCTGGTGCTCTATTTCTTATCACCATACAGGT CTCTAAGGTCACCTTTAGGTCTAACATTGTATGAA TGATTGTCAGCAACTTTCCAATTTTTTTCATATAC ATATATTTTTTTTATTTTATTTTTTACTTTTTCTT TTTTTGAGACAGGATCTCACTCTGTCACCCAGGCT GGAGTGCAGTGGCGTGATCATAGCTCACTGTAGCT TCAACCTCCTGGGCACAAGTGATCCTCCCACCTCA GCTTCCAAGGTACCTGTGACTACAGGAATGCGCCA CCATGCCCGGCTAATTTTGTTATATATATATATAT ATATATTTGTACCTTGGTTTTCTCATCTGTAACAC CAGGGGTTGAAGTGCTGTGATATTTTTTGGTTCTA GGATAATTTGGAAATAGGGATCTCTTAACATCTTG GATACTGCCAATAGATCATTCACGAAATCCCTTTA GATGAGTGTTATGTTTACTTAGGTCTCTAAAACAA TTTGTAAGGTCAACAGATGGGGATAAGAATGACCT GAAGCTGGTCGTCTTTGTTCGCAACCAGAAACAGT CCTGCCTCAAAAAAAAAAAAAAAAAAAAGGGAGTA GGCAGGTGGCCATATTTGTTTCTGGCAAGTGAGTG CTGAAGGAAAGGAGCTGAAGCCTCCCACAGTCATA ACTGGTGCTGGCAGGCTACTGTCTCGGTCTTGGGC GCCACTGATCTAAGGTCACGGCTCTGCTTGCTGCT CCCACCCGCTCCAGTTTAAAACCTGCGGTTCCAGG GTTCTCCAGCCCCTCCCTTTTTCACGCTCCGAAGC CGAGAAGGCCCAAAGCGAAGACAGAGAGGACCCGG AAGTAGGGAAAACCTCTGAGCACGTGATGGGGGAA CACGCGGGTGCTGT

ATGGGAGGTTGTGCTGGTTCTCGACGCCGGTTCTC AGATAGTGAGGGGGAGGAAACGGTGCCCGAGCCTC GGCTTCCACTTCTGGACCATCAAGGCGCTCATTGG AAGAATGCAGTCGGGTTTTGGCTCCTCGGTCTCTG CAACAATTTCTCTTACGTGGTCATGTTGAGCGCTG CCCATGACATTCTTAGTCATAAAAGAACCTCAGGC AATCAGTCCCACGTTGATCCAGGTCCAACACCTAT TCCTCATAACTCTAGCAGCAGATTTGACTGTAATA GTGTTAGCACAGCTGCAGTGCTGCTCGCTGATATA CTTCCGACGCTTGTTATAAAGTTGTTGGCTCCTCT GGGATTGCACTTGCTGCCCTATAGTCCCCGAGTCT TGGTTTCTGGCATTTGTGCTGCCGGCTCATTTGTC TTGGTGGCTTTCAGTCACAGTGTGGGGACCAGTCT GTGTGGAGTCGTGTTCGCATCAATTAGCTCTGGAC TGGGCGAAGTAACCTTCCTGTCCCTCACAGCCTTT TATCCGCGCGCCGTAATTAGTTGGTGGTCATCTGG AACCGGCGGCGCGGGGCTGCTCGGCGCCCTTAGCT ACCTGGGATTGACTCAGGCGGGGTTGTCACCACAA CAGACTCTCCTTAGCATGCTTGGCATTCCAGCCTT GCTTCTGGCTTCTTACTTTCTGCTCCTTACGTCCC CGGAAGCGCAGGACCCTGGCGGTGAAGAGGAGGCG GAGTCCGCCGCTCGACAGCCACTCATTCGAACTGA AGCTCCCGAGTCCAAACCAGGAAGCTCTTCCTCCC TCTCCCTGCGGGAACGGTGGACAGTCTTTAAGGGA CTGCTGTGGTACATAGTGCCTCTTGTGGTAGTGTA TTTCGCGGAATACTTCATAAACCAGGGTCTTTTTG AGCTTCTTTTTTTTTGGAATACAAGCCTGTCACAC GCCCAGCAGTACCGATGGTATCAGATGCTGTACCA GGCGGGGGTTTTCGCTAGCCGATCCTCCCTGCGGT GCTGCAGGATTCGATTCACTTGGGCTCTCGCGTTG CTGCAATGCTTGAACCTCGTTTTCCTTCTCGCAGA CGTCTGGTTCGGTTTTCTCCCTAGTATCTATCTGG TCTTTTTGATTATATTGTATGAAGGTCTTCTGGGA GGAGCGGCATACGTGAATACTTTTCACAATATCGC CCTTGAGACTTCCGACGAGCATCGGGAATTTGCCA TGGCGGCGACGTGTATCTCCGATACCCTGGGTATA AGCCTGAGTGGACTGCTCGCGCTTCCGCTCCACGA TTTTCTGTGTCAATTGAGCGATTATAAAGATGATG ATGACAAATA

The CLN3 protein sequence is:

(SEQ ID NO: 5) MGGCAGSRRRFSDSEGEETVPEPRLPLLDHQGAHWKNAVGFWLLGLCNNF SYVVMLSAAHDILSHKRTSGNQSHVDPGPTPIPHNSSSRFDCNSVSTAAV LLADILPTLVIKLLAPLGLHLLPYSPRVLVSGICAAGSFVLVAFSHSVGT SLCGVVFASISSGLGEVTFLSLTAFYPRAVISWWSSGTGGAGLLGALSYL GLTQAGLSPQQTLLSMLGIPALLLASYFLLLTSPEAQDPGGEEEAESAAR QPLIRTEAPESKPGSSSSLSLRERWTVFKGLLWYIVPLVVVYFAEYFINQ GLFELLFFWNTSLSHAQQYRWYQMLYQAGVFASRSSLRCCRIRFTWALAL LQCLNLVFLLADVWFGFLPSIYLVFLIILYEGLLGGAAYVNTFHNIALET SDEHREFAMAATCISDTLGISLSGLLALPLHDFLCQLSDYKDDDDK 

Conservative changes to the CLN3 protein sequence above (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 conservative residue changes, or up to 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% conservative residue changes) that result in a functional equivalent version of the protein (e.g., that retains at least 70%, 75%, 80%, 85%, 90%, 95%, 97%, 99% of the wild-type enzyme activity) are also within the scope of the invention.

Likewise, in any of the nucleotide sequence encoding the protein and variants thereof, such as in SEQ ID NO: 4, nucleotide sequence changes that do not result in sequence change of the encoded protein in SEQ ID NO: 5 due to, for example, codon degeneracy, are within the scope of the invention. Further, codon optimization of any of the polynucleotide sequence for optimal expression in a specific type of host cell is also within the scope of the invention.

Numerous other neuronal diseases/disorders can be similarly treated by the constructs, AAV vectors, and methods of the invention. A representative (non-limiting) list of the treatable diseases and disorders, along with the corresponding GOI's, are provides in the table below.

Target No. Diseases Target Gene (GOI) GOI Size 1 Ceroid-Lipofuscinosis CLN3 1403 2 Fucosidosis FUCA1 1487 3 Giant Axonal Neuropathy GAN 1880 4 Globoid cell leukodystrophy GALC 2144 5 Mucolipidiosis Type IV MCOLN1 1829 6 Neuronal Ceroid Lipofusinoses PPT1 1007 7 Niemann-Pick Disease SMPD1 1982 8 Sandhoff Disease HEXB 1757 9 Sanfilippo syndrome SGSH 1595 10 Tay-Sachs Disease HEXA 1676 11 Hunter Syndrome IDS 1739 12 Sialidosis NEU1 1334 13 Multiple Sulfatase Deficiency SUMF1 941 14 Childhood Epilepsy GAT1/SLCA1 1886 15 CMT Peripheral Neuropathy FIG4 2810 16 Neuronal Ceroid Lipofusinoses CLN5 1163 17 Aspartylglycosaminuria AGA 1127 18 Mucopolysaccharidoses IDUA 2048 19 Parkinsons Disease/Symptoms GDNF 722 20 GM1-Gangliosidosis GLB1 2120 21 Charcot-Marie-Tooth Type 1A PMP22/MFN2 569 22 Retts Syndrome MECP2 1583 23 Dannon Disease LAMP2 1322 24 Mucopolysaccharidoses NAGLU 2318 25 Mucopolysaccharidoses ARSB 1688 26 Sly Syndrome GUSB 2042 27 Biotin basal ganglia disease SLC19A3 1577 28 Pelizaeus-Merzbacher disease PLP1 920 29 Neuronal Ceroid Lipofusinoses TPP1/CLN2 1778 30 Canavan Disease ACY2/ASPA 1028 31 Beta-Mannosidosis MANBA 2726 32 Wolman Disease LIPA 1286 33 Cystinosis CTNS 1289 34 Mucopolysaccharidoses GNS 1745 35 Mucopolysaccharidoses HGSNAT 1994 36 Alzheimer's Disease/Symptom NeuroD1 1157 37 Salla Disease SLC17A5 1574 38 Jansky-Bielschowsky disease CLN6 1022 39 Neuronal ceroid lipofuscinoses CLN8 947 40 GM2 gangliosidosis GM2A 668

The sequences of the above genes that can be included in the viral vectors as GOI's are provided below.

The FUCA1 protein sequence is:

(SEQ ID NO: 6) MRAPGMRSRPAGPALLLLLLFLGAAESVRRAQPPRRYTPDWPSLDSRPLP AWFDEAKFGVFIHWGVFSVPAWGSEWFWWHWQGEGRPQYQRFMRDNYPPG FSYADFGPQFTARFFHPEEWADLFQAAGAKYVVLTTKHHEGFTNWPSPVS WNWNSKDVGPHRDLVGELGTALRKRNIRYGLYHSLLEWFHPLYLLDKKNG FKTQHFVSAKTMPELYDLVNSYKPDLIWSDGEWECPDTYWNSTNFLSWLY NDSPVKDEVVVNDRWGQNCSCHHGGYYNCEDKFKPQSLPDHKWEMCTSID KFSWGYRRDMALSDVTEESEIISELVQTVSLGGNYLLNIGPTKDGLIVPI FQERLLAVGKWLSINGEAIYASKPWRVQWEKNTTSVWYTSKGSAVYAIFL HWPENGVLNLESPITTSTTKITMLGIQGDLKWSTDPDKGLFISLPQLPPS AVPAEFAWTIKLTGVKDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for FUCA1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

FUCA1-DNA

(SEQ ID NO: 7) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC AATAATGACGTATGTTCCCATAGTAACGCCAATAG GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA TCATATGCCAAGTACGCCCCCTATTGACGTCAATG ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT CTACGTATTAGTCATCGCTATTACCATG CCCATCTGTATTAAAAATACAAAAATTAGCCAGGC GTGGTGGCGTACCTGTAAACCCAGCTACTCGGGAG GCTGAGGCAGGAGAATGGCTTGAACCCAGGAGGTG GAGGTTGCAGTGAGCTGAGATTGCAGCACTGCATT CCAGCCTGGGCGACAGAGCAAGACTGCATCTCAAA AGAAAAGAAAAGAAAAAAGAAAAGAAAAGAAAAGA AAACAGCTGTGATTCAGCAATAGTCATTTTCTCTC CTTGTCACTGCCAGAGTGAGGAAGTGCTGGGTTCT GTCAACATAGGCTCTGACTTCTCATGAGGTGCAAG AAAGAAGCAGCATGAACAAAGGCATAGATTTTGCA CCTGGAGACACGTATTCTAGTCCCACCTCTGACTC AAACTAGCTGCATGATCTTGGGCAGCCCCCCAGCC CTCTCTGGGCTTCAGTTCCCTCCTCGGTACAATGG GAAGGGTAGGGAAGAGGATGGTGCCTAGGATCTTC AAAGTCCCAACTCTGATGTGCTGCCATTCTCTCAC TGGCATGTGGGAACTGAGTGTGCTACGTGGAGTCA TGAGACTTCTTCTTCCTTTTCTTTTTCTTTTTTTT TTTTTTTTTTTTTGAGACCGAGTCTCACTCTGTCG CCCAGGCTGGAGTGCAGTGGTGCGATCTCGGCTCA CTGTAACCTCCACCTCCCGAGTTCAAGCAATTCTC CTGCCTCAGCCTCCTGAGTAGCTGGGATTACAGGC GCACCCCATGCCCGGCTAATTTTTGTATTTTTAGT AGAGATGGGGTTTCACCATGTTGGCCAGGCTGGTC TCAAACTCCCGACCTCAGGTGATCTGCCCACCTCG GCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCA CCTTGTCTGTTCAGAGACTTCTGACTTCCGTATTT CCCTCGCTAATGGCCTCACCTCCCGTTTGAGTATG TGCAGCATGTGCAAATTGCAGAGGAACTGGGGAAC TTCCCTGCCAGGCAATCCTGGGTCCTCTTGGCTCT CCACTTCCTCCTTCCTTCCTTCCTTCCTCCTTCCT TCCTTCCTTCCTTCCTTTCTTTCTTCCTTGGTCTG GCTCTGTCGCCCAGGGGCTGGAGTGCAGTGGCGGT ATCTCGGTACAAACTAAGCTATTTGAAATGCCTCG GAATTCCCAAAGAAAGCTCAGTAAATACCAGACAG ATGAAACGGTCCTGCCCGCTCTCCCTCTTTCAGTA CCCAGTTTTCTCTTTCCTCTCCTTTCATAACGTTT CTTCCCATCATCCCTCTACCTCCTTATTTCTGTCA GGGCTGTTAGATACCCTTCCGGTCTGTTATCTCCT CCTCCAGCCTTGTGCTACAGGACAACTCAAAAGCC CCCTATGGCTCCCAAGTGATCACTAAATAAAACTC GTGATCTCACTTCAGCCTACCCCTGCAGGATTGCT GCGGCAAAATGGACTACTCCCAGAGGCGTGATCAC GGTTCGGTTCACTGCAGCCCAGACTTCCCGGGCTC AAGCGATCCCGAACCTCCCACCTCAGCCTCTCGAG TAGCTGGGACTCCAGACGTGCACCACTACGCCAGG CTCATTTTGTTTATTTTTTATAGAGACAGGCTAGT CTCCAACTTGTGGGCTCAGAGCGATCCTCCCGCCT CGACTTCCGAAAGTGTTAGGATTACAGGCGTGAGC CACTGCGTCCGGCTCAATGGACTCCTTCTTAAATG TGAGTTCTCCGCACACACTGGGCCTTGCTCACCTC CACGATTTAACCTCGCAGTTAAGTCCCTTTTCAAG GTTTTTATTCGTCCTTCAGCGAAGCGCTGTCAACG CCTCCCTGCGTCTTTCCCTTCTTGAGCACCAGAGG GCGCTCCTCCGACCCGAGGAGGAAGCGACTCGGGC CAACCTGTCCAGGTTGTCCCACCCCTTTTTCCTTC CGGGCCAATCGTTAGTCAGAGTGGGCGGAGCCGCC CGCGGGCACCTGCGCGTTAAGAGTGGGCCGCGTCG CTGAGGGG

ATGAGAGCACCCGGCATGCGATCAAGGCCCGCAGG GCCAGCTCTCCTCCTCCTGCTCCTTTTTTTGGGGG CTGCAGAATCTGTAAGAAGAGCTCAACCCCCAAGG AGGTACACTCCTGATTGGCCCTCATTGGACTCACG CCCACTCCCGGCGTGGTTTGATGAAGCTAAGTTCG GAGTGTTTATCCATTGGGGTGTATTCAGCGTGCCC GCGTGGGGGTCTGAGTGGTTTTGGTGGCACTGGCA AGGAGAGGGCCGCCCGCAATACCAGCGATTCATGA GGGACAATTATCCTCCAGGCTTCTCATACGCTGAC TTCGGTCCTCAGTTTACAGCTAGATTCTTCCATCC AGAGGAGTGGGCCGATCTTTTCCAGGCGGCTGGAG CTAAGTACGTCGTTCTGACGACAAAGCACCATGAA GGGTTCACCAACTGGCCAAGTCCAGTGTCCTGGAA CTGGAACAGTAAGGATGTCGGTCCTCATCGGGATC TGGTAGGCGAACTTGGGACTGCTCTCCGGAAGCGC AATATACGCTATGGTCTTTATCACAGTCTGCTGGA ATGGTTCCACCCACTGTACTTGCTGGACAAGAAGA ACGGATTTAAAACCCAACATTTTGTTAGCGCAAAG CATATGCCAGAGTTGTACGACCTGGTAAATTCCTA TAAACCCGACCTCATCTGGAGCGACGGAGAATGGG AGTGCCCGGATACTTATTGGAACTCAACTAACTTT CTCTCCTGGCTGTATAATGACTCCCCTGTGAAGGA CGAAGTTGTTGTAAATGACAGATGGGGTCAAAACT GCTCATGTCATCACGGGGGATACTATAATTGCGAA GACAAGTTTAAGCCTCAATCTCTTCCCGATCATAA ATGGGAGATGTGTACTTCTATTGACAAGTTTAGTT GGGGATACAGGCGCGACATGGCCTTGTCTGATGTT ACGGAGGAATCAGAAATCATCTCCGAGCTGGTACA AACGGTGTCATTGGGAGGCAACTACCTGCTGAACA TAGGCCCAACGAAAGACGGGCTTATCGTGCCGATT TTTCAAGAACGCCTTCTCGCAGTTGGCAAATGGCT CTCTATTAATGGGGAAGCTATTTACGCGTCAAAAC CTTGGAGGGTCCAATGGGAGAAAAACACCACTAGT GTATGGTACACAAGCAAAGGAAGCGCCGTCTACGC TATCTTCCTGCACTGGCCAGAGAATGGCGTACTCA ATTTGGAATCACCTATAACCACATCCACGACTAAG ATCACCATGCTCGGGATTCAAGGTGACCTTAAATG GTCTACAGACCCAGATAAAGGTCTTTTTATTAGTC TTCCCCAGCTGCCTCCCAGCGCGGTTCCGGCCGAG TTCGCCTGGACGATCAAGCTGACCGGGGTTAAAGA CTATAAAGACGATGATGATAAATA

The GALC protein sequence is:

(SEQ ID NO: 8) MAEWLLSASWQRRAKAMTAAAGSAGRAAVPLLLCALLAPGGAYVLDDSDG LGREFDGIGAVSGGGATSRLLVNYPEPYRSQILDYLFKPNFGASLHILKV EIGGDGQTTDGTEPSHMHYALDENYFRGYEWWLMKEAKKRNPNITLIGLP WSFPGWLGKGFDWPYVNLQLTAYYVVTWIVGAKRYHDLDIDYIGIWNERS YNANYIKILRKMLNYQGLQRVKIIASDNLWESISASMLLDAELFKVVDVI GAHYPGTHSAKDAKLTGKKLWSSEDFSTLNSDMGAGCWGRILNQNYINGY MTSTIAWNLVASYYEQLPYGRCGLMTAQEPWSGHYVVESPVWVSAHTTQF TQPGWYYLKTVGHLEKGGSYVALTDGLGNLTIIIETMSHKHSKCIRPFLP YFNVSQQFATFVLKGSFSEIPELQVWYTKLGKTSERFLFKQLDSLWLLDS DGSFTLSLHEDELFTLTTLTTGRKGSYPLPPKSQPFPSTYKDDFNVDYPF FSEAPNFADQTGVFEYFTNIEDPGEHHFTLRQVLNQRPITWAADASNTIS IIGDYNWTNLTIKCDVYIETPDTGGVFIAGRVNKGGILIRSARGIFFWIF ANGSYRVTGDLAGWIIYALGRVEVTAKKWYTLTLTIKGHFTSGMLNDKSL WTDIPVNFPKNGWAAIGTHSFEFAQFDNFLVEATRDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GALC and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

GALC-DNA

(SEQ ID NO: 9) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG TCCTCTGTCATCACCTTGGTATTTCCCATC TAGTCACGGTATTAAGTGGGTCTTATGCGCTTGTTAAGAGCTGGTAAGAGAAGCTTAACATTCACTTG ATGGAATGGTTACTGTGGCTTGTATCCACAGGAGCTCCAGCTCATGCTTAAAATACTGTGTTAGAACA AATGGATCAGAGTGAATTCTGTAACAGTAAATCCACAGAACTGAAAATTACTGACTTGCATCATAAAC TGGTTGCAGTGGCAAGGCAGAGAGTTCAGATTCGTGTTGTACTGGGGAAAGAAGAAACCAAAGAAAAT AAGTGGTTCATACACAGGGGACTATTTAACTGATCCAAGCCAGAAGACTACTGAGGGTGAAAGGAGCA TTATCAGTAATTATGTTTAGACAAAAGTTGTGACTGTCCTTAGTAAACCAGGATAGACGTAGAGTCAA TTCAAAAAGAAAGAAAGAACAAACATATCTAATGTACATTAAGAACCCAGGGATATCGGGTTCTTAAT GTGCATATTTATTGGATTGCCCAGAGCTTTGACCTTCAAGTATAATTGAGTTCTTGAAACTTAGATTT AGGTTTGTGGTTAAGGGGCAAAATAATCAGATTCCAAATAGGGTTCTGCAGACAAATCCCACAGGTCC TAAAGTCTCTGGGTCTTTTCCTTGCCATTGTGGTATCTCAGGGGCTTGTGTAGGCAATGATAACCAGT TCCATACTTCTGCTAAGAGAAATTTGGGGATCAGAAAATCTTTCTCTGCAGCTCTTCAGAGTCTCTTT AATTTACTTCAATAACAAGGAAATCAGAAATCTCAGGACAGTGCTGGATGTGGCAGAAATTCAGGGCA ATTCACAACTTTCCTACCAATTTAGAGTTACCTGTCTGGAATCACTTCAACTGACAGTGGAAGATAGT TTATAAAATTGTAGGGGAGGCAAAATTTCACCTTCGTCCCTGTAGGGTCCCAGCATGGCCCTAGTATT AAATTGATTTAAGATATTAATAGACTGACAGGAGACAACCACACAAATGTTTATTTTACATAGCACGG GGGCCCTCATTAAAAAAAAAAAAGACCTAAAGCAGCAGTTAAGAGCCAATTGCTTATAGAGTGAAATG GACAAAAAATAGTAGTTGTGAAACATGATAAGGCGAAGGGGCTTGGGGTAAAGAAGCGACTAGAAAGA TAGGGATTAACAAATTTTGTTTGGACAGATTTCCCTCGACTTCAACTTTCTGTCCTTGAAGATAACAA TGTTATTTTATAGGGAAGACATCTTTCACATGGGAATTTCATCTCCTCCTTTTAAGACACATAATATC CATGACAGTGATCTTGCACCTGCTGTTTTTAAGTGCCTTTAATTTAAAATAGTCAATATGCCACAGCA GCATATTTTGAGGTGGTATATTATTAACTCCTTCAAGGCTAAAAGCTTTGAATATGCCGGGGTAGTTA CCAGACTGGAGAACCTTCTCAGCTATTTGCCACTTGTGGAATGCATTCAAATGTACTGAGTGCTTATT AACTTTTCTCTCAGTCCCTCACTCTGCTGCTCTTCTCGCCTCATCTCACATAAGGGAAAACTCAGGCT CCAAAAGCAAAGTGATTCCACCAAGATGACAATGGAATCGGGACCTGGTGTCCAAGCCTGGTCCTCGC ACGAGGTAGATACTCCCTGAGATGCTGGGGAAGAGCCATGGTAGGGCCACTCATGGCCCTCTTCCTTT GGCGGACCTTGGAATCCACCTTCCCTGCGTTAAAGTGCTCCACCAGGTGACGCCGGAAGAGAAGCCAG CAGTAAGTACATGTGAAATCCAGTAGCTGACCACAGACACGCGAGCGATAAGAAAAAGCTCGCTGCTT CTTTTCTCAACACTCCGCCAGCTGCGTCAGAGGCCCTTGACCCGCACTCAAAATGGCGGCGGCGGCGT CAGCATCAGCGGCCTCCTGCCCGTATCTATCGTGGCGGCGACGGGACCCGCCTCCCTGGGCGCCGG

ATGGCCGAATGGCTCCTTTCAGGATCATGGCAGCGCCGA GCTAAAGCGATGACGGCTGCCGCGGGCTCTGCTGGGAGAGCAGCTGTTCCTCTTCTGCTTTGTGCCTT GTTGGCACCTGGCGGAGCCTACGTTTTGGATGACTCTGATGGATTGGGTCGCGAGTTCGATGGTATCG GTGCTGTGTCTGGTGGCGGAGCCACGTCCAGGCTGCTGGTAAATTACCCGGAACCATATCGAAGCCAA ATCCTTGACTATCTTTTCAAACCTAACTTTGGAGCGAGCCTTCATATTCTCAAGGTCGAAATAGGCGG AGACGGGCAGACAACTGATGGCACCGAGCCGTCTCATATGCATTACGCTTTGGACGAAAATTACTTTA GAGGATACGAATGGTGGCTGATGAAGGAAGCCAAGAAAAGAAATCCCAATATTACCTTGATCGGCTTG CCGTGGTCATTTCCCGGGTGGCTGGGCAAGGGATTTGATTGGCCGTATGTAAATCTTCAATTGACGGC CTATTACGTAGTTACATGGATAGTAGGTGCCAAACGCTACCATGACCTGGATATTGATTACATTGGAA TTTGGAACGAACGATCCTATAACGCAAATTACATCAAAATTCTCCGAAAGATGCTCAACTATCAAGGC CTCCAGAGAGTTAAAATCATCGCGTCAGATAACCTTTGGGAGTCTATTTCTGCCTCAATGCTGCTCGA CGCGGAACTTTTTAAGGTGGTTGACGTTATAGGGGCGCATTATCCAGGTACCCACAGCGCTAAAGACG CAAAGCTCACGGGCAAAAAGCTGTGGAGCAGTGAGGACTTTAGTACCTTGAATAGTGACATGGGTGCA GGGTGTTGGGGTAGGATACTGAACCAGAATTACATCAATGGATATATGACGAGCACTATAGCATGGAA CTTGGTAGCGAGTTATTACGAGCAGTTGCCGTACGGTCGATGTGGTCTTATGACGGCGCAAGAACCGT GGAGCGGGCACTATGTGGTCGAGAGTCCCGTTTGGGTAAGCGCTCATACAACTCAATTCACGCAGCCT GGGTGGTATTATCTCAAGACCGTTGGACACCTTGAGAAAGGCGGGAGTTACGTAGCACTTACCGACGG CTTGGGGAACTTGACTATTATCATTGAAACAATGAGTCACAAACACAGCAAATGTATTAGGCCTTTCC TGCCATATTTTAATGTCTCTCAGCAGTTCGCTACTTTTGTGCTTAAAGGAAGCTTCAGTGAAATACCC GAGCTCCAAGTGTGGTATACCAAACTTGGTAAAACTAGTGAACGATTTCTTTTCAAACAACTCGACTC ACTTTGGCTGCTTGACTCTGACGGAAGCTTCACTCTCTCTCTTCACGAAGACGAGTTGTTTACTCTCA CTACGCTTACTACTGGACGCAAGGGTTCATATCCTCTTCCTCCAAAATCTCAGCCATTCCCTTCCACA TATAAGGATGATTTTAACGTCGATTATCCCTTCTTCTCCGAAGCGCCGAATTTTGCGGACCAAACAGG TGTATTTGAATATTTTACTAACATTGAGGACCCAGGAGAGCATCACTTCACCTTGCGACAGGTCTTGA ACCAGAGACCAATCACTTGGGCAGCCGACGCCTCTAATACCATATCAATTATCGGTGATTACAACTGG ACTAATCTCACAATTAAATGTGATGTCTATATTGAAACTCCTGACACTGGAGGTGTTTTCATCGCCGG GCGCGTCAACAAAGGAGGTATCCTTATCCGATCAGCTCGCGGTATCTTTTTTTGGATTTTTGCGAATG GAAGCTACCGAGTTACAGGTGATCTTGCTGGGTGGATTATCTACGCCCTCGGCAGAGTAGAGGTTACT GCCAAAAAATGGTATACTTTGACGCTGACGATCAAGGGCCACTTCACAAGTGGTATGCTTAACGATAA AAGCCTGTGGACGGACATTCCAGTGAACTTTCCTAAGAACGGTTGGGCCGCCATTGGGACACACTCAT TCGAATTTGCCCAATTCGATAATTTTCTCGTGGAGGCAACCAGAGATTACAAGGATGATGATGACAAA TA

The MCOLN1 protein sequence is:

(SEQ ID NO: 10) MTAPAGPRGSETERLLTPNPGYGTQAGPSPAPPT PPEEEDLRRRLKYFFMSPCDKFRAKGRKPCKLML QVVKILVVTVQLILFGLSNQLAVTFREENTIAFR HLFLLGYSDGADDTFAAYTREQLYQAIFHAVDQY LALPDVSLGRYAYVRGGGDPWTNGSGLALCQRYY HRGHVDPANDTFDIDPMVVTDCIQVDPPERPPPP PSDDLTLLESSSSYKNLTLKFHKLVNVTIHFRLK TINLQSLINNEIPDCYTFSVLITFDNKAHSGRIP ISLETQAHIQECKHPSVFQHGDNSFRLLFDVVVI LTCSLSFLLCARSLLRGFLLQNEFVGFMWRQRGR VISLWERLEFVNGWYILLVTSDVLTISGTIMKIG IEAKNLASYDVCSILLGTSTLLVWVGVIRYLTFF HNYNILIATLRVALPSVMRFCCCVAVIYLGYCFC GWIVLGPYHVKFRSLSMVSECLFSLINGDDMFVT FAAMQAQQGRSSLVWLFSQLYLYSFISLFIYMVL SLFIALITGAYDTIKHPGGAGAEESELQAYIAQC ODSPTSGKFRRGSGSACSLLCCCGRDPSEEHSLL VNDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for MCOLN1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

MCOLN1-DNA

(SEQ ID NO: 11) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG ACCCTGACCCTGGCTCTGGGCCGGGCACTC TGCCGGATCCCAGCTCCAAACCCCTCCCCGGCTCCAGATCCACCCCCAGCCCTACTCCTGTGGAATCT TCTGACCCAAAGGCTGGGCACGACGCTGGTCCCGACCTTGTGCCCAGCCCAGACCTTGATCCTGTGCC CAGCCCAGACCCTGATCCTGTGCCCAGCCCTGATCCCAACCCTGTGTCCTGCCCTGACCCCTGTTCTC CCACTCGTGGCACTGTCAGCCCAGCCCTCCCTACCGGCGAGAGTCCAGAGTGGGTACAGGAGCAAGGG GCACTGCTGGGGCCTGATGGCTGAAGGAGACGCCGGCATCCTCGGGGGCCTGGGGAAGTTGTGTGTTG TGCAGTCAGTAAAATCCTCCCACTGCCTCCGGGCTCTGTGTCGTGGCTTGCCTTTTGTGCTTTCTTTC TGAGCACAGCCCCTTGCTCCGGAGATGGGACATTGTGGCCAGGGCCAGCCACAATCTGGAGCTCCAGT GTCCTGGCTTCCTTCTTGGGCCCACCAGCTAGACTTTCCAGCTTAACCCACAGTGTCTCATCCTGGTC CATCCCACTAGTCACCACTCTCTGTTCCTCTCACTTACCCCTTGCTCTTCAAAGCCCATACAGTAGGT ATACAAGTGGACAAAAAAAGTTGCTCATTTATGCAATCAACAAACATCTCTGGATTGCTGGGGTCTCA GCAGGGAACAAGATAAATATGGCCTCGACCTGCATGGAGCTCATAGATACTAAATTCAGAATACTTAA AAAATAATTACGGGGTATAGTACATTCTAGGAGAAGCATAACAAGACTTCTGATATAAATGGCAGGCA GCTTTCTCAATGAAGGATTTTGTAATCCCAATAATCACTAATTTAATAATCAGTACTGTTTGCCCAGC CTTATGCGATAGTTTTTGCATTCTCTCATTTAATCCTCTCAACAGCCCCAGTAGGTAGATGACTTTGA ATATCCCCATTTTGCAAATGAGAAAATTGAGGCACATTTTTTTTTTTTTTTTTAGACAGTCTTGCTCT GTTGCCCAGGCTGGAGTGCAGTGGTGTGATCATAGCTCACTGCAGCCTCGACCTCCTGGGCTCAAGCG ATCCTCCCACCTTAGCCTCCCGAGTAGCTGGGATTGCCGGTGCATGCCACCGCCCACTGCGCTCAGCT TGGAGTTGAAGGGACTCTGGAAGATGTAGAAGTGGCATTGTCAGTGCCTAGATTTAAATCCCAATTGC CCTCCAGGGTCCAAATTCTTAACCATTACGCTCCAGGGCAAAAGTATGCAAAGGCTCTGGGGCTATAG AAAGATGAGCTTTGGATGGAGGTAGGAGCCAGATCAGAGGGCCCTGATAGACGAGAGTGGGGACTCTG CCTGTCATTACAGAGCAATGGGAAGCCGAGGGCAGGTTCTCGCAGGAAGGATAGGAATTATTCTTTGA AGATGCTTGTGGCTGCTGGGTAGAGAGTGGAGTGGAGGGAGGCTGAGATCGGGGAGGAGGTTGCTGCA AAGATCCAGGCCAGGAATGTTGGAAGACTCTGGGCTGGGGGCCATGGGGTGGGGATAAGTGGTTCTAT TTGATACATAATTAGGAAATCGTGTTTGCTGAAGATGCGCAGGAGAAGGGTAAAAGGAGTTTCTGGGA GAAAGAGGAAGACAGCGTTGAGATAGTAGGCAGGGTCATCACCAGGCACCAAGGAGGATAAGGGGTCA AGCTCTGGACATGGAAGTCACAAGCCTGGCACCGGATTCGGGGCATGGCCGGGAGCCAGGGCAGAGCT CGTCGTTGCCAAACTCAGAGTCAGCCCATCCCCCGCCACCCAGAGCGCGTCGGCGCTAGGACCTAGCG ACTGCCTTCGACCCAGAGGGCGCCGGCAGAGGCACGCATGCGCGCTGTTCCGGCAGGGGTTGTCGTGG CGCAGGGGGCGGGACCAGAGGCGGTCACGTGAGGGGCTCTGGGCTACCGGGTCACGTGACCGAGGC

ATGACTGCGCCGGCAGGTCCACGAGGGTCTGAAACAGAA CGGCTCCTTACTCCCAATCCCGGCTATGGGACACAGGCCGGTCCTAGCCCTGCCCCACCCACACCCCC TGAGGAGGAAGATCTGAGGAGACGGCTCAAGTATTTCTTCATGAGCCCGTGCGATAAATTTCGAGCTA AGGGACGAAAGCCGTGCAAGCTGATGCTCCAGGTGGTAAAGATTCTCGTAGTTACTGTGCAACTCATC CTTTTCGGTCTGTCCAATCAGTTGGCAGTCACTTTCAGAGAAGAAAACACTATCGCTTTTCGGCATCT GTTCCTGCTGGGTTATAGTGACGGTGCAGATGACACCTTCGCCGCCTACACTCGCGAACAACTTTACC AGGCTATTTTCCACGCGGTAGATCAATATCTTGCGCTCCCCGACGTTTCATTGGGGCGGTACGCCTAT GTTCGCGGAGGAGGCGATCCCTGGACCAACGGCAGTGGTCTCGCATTGTGCCAACGATACTACCACCG GGGGCACGTAGATCCCGCCAACGACACCTTCGACATAGACCCGATGGTAGTAACAGACTGTATTCAGG TGGACCCCCCCGAGAGGCCACCTCCACCACCTTCCGATGACCTGACGCTGCTCGAGAGCAGCAGTTCT TATAAGAATCTTACCCTTAAATTCCATAAATTGGTAAATGTAACCATCCATTTTCGCCTCAAAACTAT CAACCTGCAAAGCCTCATAAATAACGAAATTCCGGATTGTTACACTTTCTCTGTTTTGATAACATTCG ACAATAAGGCCCACAGCGGAAGGATTCCGATATCCCTTGAAACACAAGCACACATACAAGAATGCAAA CACCCTAGTGTCTTCCAGCATGGCGATAATAGTTTTAGACTGCTGTTCGATGTAGTTGTGATCCTTAC ATGCTCACTGTCATTCCTCCTTTGTGCACGATCACTTCTTCGGGGTTTCCTGTTGCAAAATGAGTTTG TGGGATTTATGTGGAGGCAACGAGGACGCGTCATATCTTTGTGGGAACGGCTTGAGTTCGTCAATGGA TGGTACATACTTTTGGTTACATCCGATGTGTTGACTATATCCGGTACAATTATGAAAATTGGCATTGA AGCGAAGAACCTCGCCAGTTATGACGTTTGCAGTATCCTTCTGGGAACGTCCACCCTCCTCGTATGGG TAGGAGTCATACGGTACCTGACTTTCTTCCATAACTATAATATACTGATCGCAACCCTTCGAGTCGCG CTTCCGAGCGTGATGAGGTTCTGTTGCTGCGTAGCTGTTATCTACCTGGGATACTGTTTCTGTGGATG GATCGTACTCGGCCCGTATCACGTAAAGTTCCGGTCCCTTTCTATGGTCTCCGAATGTCTTTTCAGTC TCATCAACGGTGACGATATGTTCGTCACCTTTGCTGCGATGCAAGCTCAACAAGGGAGGAGTAGTCTG GTTTGGCTTTTTAGTCAACTGTACTTGTACTCCTTTATCAGTCTTTTTATTTACATGGTGCTCTCATT GTTCATCGCACTTATCACGGGCGCCTACGACACGATTAAACATCCGGGTGGAGCCGGCGCCGAGGAAA GTGAGCTCCAAGCCTACATAGCGCAATGTCAAGATTCCCCGACCTCAGGCAAGTTCAGGAGAGGCTCC GGAAGCGCCTGTTCTTTGCTTTGCTGTTGCGGGAGAGACCCATCCGAAGAGCACTCCTTGCTGGTCAA TGACTATAAAGATGACGACGATAAATA

The PPT1 protein sequence is:

(SEQ ID NO: 12) MASPGCLWLLAVALLPWTCASRALQHLDPPAPLP LVIWHGMGDSCCNPLSMGAIKKMVEKKIPGIYVL SLEIGKTLMEDVENSFFLNVNSQVTTVCQALAKD PKLQQGYNAMGFSQGGQFLRAVAQRCPSPPMINL ISVGGQHQGVFGLPRCPGESSHICDFIRKTLNAG AYSKVVQERLVQAEYWHDPIKEDVYRNHSIFLAD INQERGINESYKKNLMALKKFVMVKFLNDSIVDP VDSEWFGFYRSGQAKETIPLQETSLYTQDRLGLK EMDNAGQLVFLATEGDHLOLSEEWFYAHIIPFLG DYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for PPT1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

PPT1-DNA

(SEQ ID NO: 13) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG TGGTCTGGCACAATGGCTCACAGCTGTGAT CCTAGAACTTTGGGAGGCTGAGGGGGGCGGATTGCCTGAGCTCAGGAGTTCGAGACCAGCCTGGGCAA CATGGCGAAACCCTGTCTCTACAAAAAACACAAAAAATTAGCGGGGCATGTTGGTGGTGTGTCTGTAA TCCCAGCTACTCGGGAGGCAGAGGCACGAGAATCGCTTGAACCCGGGAGGTGGAGGTTACAGTGAGCC AAGATCACGCCACTGCACTCCAGTCTGGGGGACAGAACAAGACCCTGTCTCAAAAAAAAAAAAAAATT GCATTCAGATTGCTTCACAAGTGTCTTTCAGTTATTGCTCCAGTTTAAAGAAACCTTTAAAGAAATTA TAAATAGTTCATTAAAGGCAGGAAACTTCATTGAGCGGGCTATATTCACAGAAAAATCCTGAAACTAC TTCAATTTGTAAGTCTTAAGTTAAAATAAAATGCTTATACAATAAGCTTATTTTTCTTAAAACAAAAC TGTATACTGTACTGTATAATGCTTTATGATTCTGCATTTTTTTTTCTTTGAGACAGAGTTTCACTCTT GTTGCCCAGGCTGGAGTGCAGTAGCTCAATCTTGGCTCACTGCACCCTCTGCCTCCTGGGTTCAAGTG ATTCTCCTGTCTCAGCCTCCTGAGTAGCTGGGATTACAGGCACCCACCACCATGCCCGGCTAATTTTT TGTATTTTTAGTAGAGATGGGGTTTCATCATGTTGGCCAGGCTGGTCTCAAACTCCCAACCTCAGGTG ATCCACCTGCCTCAGCCTCCCAAAGTGCGCCCAGTGGATTCTGCATTTTAATCGACTTTTCAACTAAC AACTTACCTCTAGTCCCAATGGCATGGAATAGAAGAGATTACAGACCGTGGGTTTGTAATCGACTTTT CTTTTACAACATATTAAGGGCATTTTTCATGTCACTTTATGTAAATTTACCTCATTTTTCTTTTTTGA GAGAGACAGGGTCTCACTGTTGCCCAGGGCAACAGCGAGATCATAGCTCAGTGCAATGGCGAGATCAT AGCTCAATGCAGCCTTGAACTCCTGGGCTCAAGTGATCCTCCCACCTTAGCCTCCCCAGTAGCTAGGA TTACAGGCACATACCACCACCCCTGGCTAATTAAAAAAAAATTTTTTTTTTGTAGAGATGGGGTCTTG CTATGCTGCCTGGGCTGTACTCTCTTTTTATTTATTTTTTATTCTTATTTTTTGAGACAGAGTTTTGC TCTTGTTGCCCAGGCTGGAGTACAATGGTATGATCTCAGCTTACCGCAACCTCTGCCTCCCGGGTTCA AGAGATTCTCCTGCCTCAGCCTCCTGAGTAGCTGGGATTACAAGTATGCGCCACCACACCCGGCTAAT TTTGTAATTTTAGTAGAGACGGGATTTCTCCATGTTGGTCAGGCTGGTCTCGAACTCGCTACCTTAGA TGATCTGCCCACCTCAGCCTCCCAAAGTGCTGGGATTACAGGAGTGAGCCACCGCGCCCGGCCCTATA CTCATTTTTTATAAAACTGGCCTCATATTATTCCATTGTATAGTGGATACACTCTAATTTCTTTATAA ATTATTTAAACTATTTTTTGATGTTTTGTTGAAAAAAAACTTGAGCAGGGAACTGATATTATGAAGGT GGATTGAGGGATGAATGTGGCAATAGAGCATAAAATGAATTAAAGAGGAGAGAATGGAAAAGGAAATG GTTGATGAGAGACCCTTGAAATAATCCAGCTGAGATTAGGCCAGTTAGTGGCCATGGGTTTCCCCCTC ACTCTTATGCATCCAACATATGCTTTCGTCCGTCTTGAAGTCCCGACATTTCTAGAAAACACAGTTGT CTTTCTCCTCTCTACCTTAGCTCATCTCAGTCCTTCTGAATTTCATCTTTGCTTGTTGAAATCCTACC TCTCCTTCAATATCCAGAACAAACCCCACACCCTGCCATGATTGGTCCTGGCTGGAAACCGTCCCTCC TTCTTTCTTCCTTCCTCTGTGCATGTTTCTTGCAAAGGCAGTACAGGGCAGTGGTGAAGAGCAACGAC TTTGGAACCACCAATTTGCTATCTCTGTGACCTTGGGCACCTTACTCAGTGCCAATTCGCAGTGCCTC AGTGTCCTCACCTGTCAGGGGGAGAAGTGCATACAGCATTGTTATGAAGAGTGAATTAGTTAAAGGTT GTAAGAATAGTGCCTGATAGCATCTGATCAGCACTGAATATATGTTAGCAATTATTTTGATTCACCGC AGAGGGCGGTCTACGAGAGCGCAGAGCCCCACTCGGCCAGCGGGGTCTGGCGGGGGACCTGTCGCGCT GAAAGCTCCAGGGTAGGGCCGACGCCCATCAGGCTGGGCATCCGTTCGGGATGCGCAGGTTGCGATCT GCAACCGGCGGCGCCACGCCCAGGCGGGCGGAGCGCGGTTCCCGGAGTCTCGCGCCCGCGGTCA

ATGGCGTCTCCTGGTTGTCTTTGGTTGCTTGCCGTCGCGTT GTTGCCTTGGACATGTGCTTCTCGGGCTTTGCAGCACCTCGATCCCCCAGCCCCATTGCCTCTTGTAA TCTGGCATGGCATGGGTGATTCATGCTGTAATCCCCTCAGCATGGGGGCCATAAAGAAAATGGTAGAG AAAAAGATCCCAGGCATATACGTACTCTCACTTGAGATAGGGAAGACCTTGATGGAAGACGTTGAGAA CTCTTTTTTTCTCAATGTTAACTCCCAAGTCACTACGGTATGCCAGGCGCTGGCGAAAGATCCTAAAC TTCAACAGGGGTATAACGCCATGGGATTCTCTCAAGGTGGGCAGTTCCTTAGAGCGGTCGCCCAGAGG TGTCCATCCCCCCCAATGATTAATTTGATCAGTGTGGGTGGACAACATCAAGGCGTGTTTGGCCTCCC CAGATGTCCAGGTGAGTCATCTCATATCTGTGATTTCATCCGGAAGACATTGAACGCAGGTGCGTATT CAAAGGTAGTGCAGGAGAGGCTGGTGCAGGCTGAGTACTGGCACGACCCTATCAAGGAGGATGTCTAC CGAAATCACTCAATTTTCCTTGCAGACATCAACCAGGAGCGAGGCATTAATGAAAGCTATAAAAAGAA TTTGATGGCTTTGAAAAAATTTGTTATGGTCAAGTTCCTCAATGACTCAATAGTCGATCCGGTGGATT CCGAGTGGTTCGGGTTTTATCGGTCAGGTCAAGCGAAAGAAACAATTCCCCTTCAAGAAACGTCACTT TATACGCAGGACCGACTCGGCCTGAAGGAAATGGATAACGCTGGGCAACTGGTATTTTTGGCTACCGA GGGCGATCACCTGCAGTTGAGCGAGGAATGGTTCTACGCTCACATCATACCCTTTCTTGGGGACTACA AGGACGACGATGACAAGTA

The SMPD1 protein sequence is:

(SEQ ID NO: 14) MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMG LVLALALALALALALSDSRVLWAPAEAHPLSPQG HPARLHRIVPRLRDVFGWGNLTCPICKGLFTAIN LGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSI VHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHW DIFSSWNISLPTVPKPPPKPPSPPAPGAPVSRIL FLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPA SRPGAGYWGEYSKCDLPLRTLESLLSGLGPAGPF DMVYWTGDIPAHDVWHQTRQDQLRALTTVTALVR KFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSS RWLYEAMAKAWEPWLPAEALRTLRIGGFYALSPY PGLRLISLNMNFCSRENFWLLINSTDPAGQLQWL VGELQAAEDRGDKVHIIGHIPPGHCLKSWSWNYY RIVARYENTLAAQFFGHTHVDEFEVFYDEETLSR PLAVAFLAPSATTYIGLNPGYRVYQIDGNYSGSS HVVLDHETYILNLTQANIPGAIPHWQLLYRARET YGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHK GHPPSEPCGTPCRLATLCAQLSARADSPALCRHL MPDGSLPEAQSLWPRPLFCDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SMPD1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

SMPD1-DNA

(SEQ ID NO: 15) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG AGCACTTACTAGCTAGCTGTGGGATCTTGA GCCACTTACTTAATCCTACTTTCCTTCTCCGTAAAATGGGGATAATTATAATACCGACTTCCAAATTT GTTGTGAGGATTAACGTAAGGCAGAGTCCTCAGAAAAGTACCTACAGAGGGTTATTCGGGCCAAGGGC CAAGGTTGAGGACTGCGACCCAGGACACACTTGCAAGTTGTCTTGGGGGAGCACTCTGGACAACAAAA GAGAGGCTCATATTTTCAAAGAAAAAAAGATGAATTAGGAGAGGAAATGAATACAAAAGTTGTTCATC AGGAATTCTCATTGTTTACAGAAATAACACTGGTTATACATTGTTTAGCGCTTGGCTATACATTGTTG AACTATAAGGTGTATGGCATTTAATGGCTACTTGGCATAGCAAGTGGTTTCAAGAGATAATTACTTAG CTCAAAGAAGAGTGAGAGTGACTGTTGCTACATTTTAAATGCCTGTCTGGGCCTGATAATTTAAAGGG GCTCATCTTCCTTAGATAAAAAGGTTTTGTTTTGTTTTGTTTTTCATAGTACATAATCTTAAAAATGC ATGCTAATTATTACTGTGAGTACTCTATCTGAGATGATGTCCCCAGAACTGGGGGGAAAAAACACTTG TAAAAAATTATCAAAGGAAAGAACTGACAGGACTTGATAGCTCTGAGGATTCCTCAGAAGCACTCGTC AAACAGCTTAGGGTTTAATTGCTATTCTGCCACTTAACTTCTTTGTGCCTCATCCTATCTGTAAAGGA GGGTAATAATAGTATTTGCAGGGACCAAGGGAAACTTTCCCTTCGCCCTCTGAAATTCTGCTGAAAAA TCAACCCACAAAAAACAGATTAATTGAAGAAAAGGCATAGAAATTGTATTAATGTGTCCACGGGGAAC CACAGAGTGACTACCCACTTCCCAGACGAGTTCAGAAGCTTAGGTGTCATTCAGGCAAAGGGGGTTGT GGGAGTGAGGGGAAGAGGAATTCTGCTGAGGGAGAAGGAATGGATCAGGGAACAGATTAACTAGCACA TTATCATGTGAAGGGGTCTGTTCAGGTGTGATTATATTCTTGGTTTTGTAGGGAGGGGAAGAAAAAAA CCGTTGTTCCTTTTGATGGGTCTGGACGCTAGGTAACGGCTTTGGGAGAGAGGGCGCGGGAGTAGGAA GGCCAGACACACCTTAAGGCTTAACTTAGTAAGTCAAACCACCATATTTTGGGTATGGATTTCTGAGC CCCAATATAATAGGTACTTCTTAGGGTTGTTGTGAGAATTGAAGATTATTAATTATAAAGTGCCTGGG TTGGTGCTTGGCACATCATAAACAACTCCATAAATGCTCGCTTTTACTGTCGTGGATACACGGAGGTG GGAGACCCAATTGGGTTCCCGCCCATGTTATTGGCCCCCACGGCTATATGGTCTTTACGGCTTCCTAG TCTCTTCACCATCTCTAAGGTTTGTTTCCTCATCTGAATCACAGGTGAGTGATTCTCAGGGTGACTCA AGAGGGCTGGTGCCAGTGGCAGAGCATGGGGAATCGAGGGAAGGCGCCTTCCTGTCAGAGGCAACACA CCCAGTGGGAGGATCCTGCCCGCCCTGCTCTCTCCTACCTCCCCTTCCCGGGCTAAACGCTGGGGTCG GTCTGGCAGCTATTCCGGGAATCTGAGCGCGGATTCTGACAAAGGAGACGTCTTCCACCGACCACATC ACATGGAGCTCCAAAGCACGAGCACGGCCTCCCGCGGCTGTGACCTCAAGGCGGAGCCCCTGGTGACC TCAGGGAGAGTCCCCACCCCCGCAGCCCGTGCGCCCGGGGCAGGGCGGGGGCAGGGAGAGGGGGCGGA ATCGGGGCGGTCCCGGGAGCGCCCCGCCCCCTCCGCCTCCGCAGCGTTGACAGCCGCCCGCCACCGAG AGATCAGCTGTCAGAGATCAGAGGAAGAGGAAGGGGCGGAGCTGCTTTGCGGCCGGCCGCGGAG

ATGCCAAGGTATGGTGCTAGCTTGAGGCAATCCTGTCCTCG CTCTGGCAGGGAACAGGGACAGGATGGTACGGCGGGAGCCCCGGGCCTGCTGTGGATGGGGCTCGTGC TTGCATTGGCGCTCGCCCTTGCTCTGGCGTTGGCACTGTCTGACAGTAGAGTCCTTTGGGCGCCTGCA GAAGCCCACCCACTGTCTCCCCAAGGGCACCCCGCCCGACTCCATCGAATCGTACCTCGCCTGCGGGA TGTTTTCGGTTGGGGCAATTTGACCTGCCCAATATGTAAAGGCCTCTTTACGGCCATCAACCTCGGTC TCAAAAAAGAACCTAATGTCGCTCGCGTTGGCTCAGTTGCCATCAAGCTGTGTAATCTGTTGAAAATA GCTCCGCCGGCAGTGTGTCAAAGTATTGTGCATCTGTTCGAGGACGATATGGTTGAGGTATGGCGACG ATCCGTCTTGTCCCCCTCTGAGGCCTGCGGGTTGCTGTTGGGGTCTACATGTGGCCATTGGGACATAT TTAGTAGTTGGAACATCTCATTGCCGACGGTCCCGAAGCCCCCTCCTAAACCTCCTAGCCCGCCAGCG CCTGGTGCCCCTGTGTCTCGGATTCTCTTTTTGACAGATCTCCACTGGGATCATGATTATTTGGAAGG GACCGACCCCGACTGTGCTGATCCTCTTTGCTGCCGCCGCGGTAGTGGACTTCCTCCTGCCTCTCGAC CAGGGGCGGGCTACTGGGGGGAGTATAGCAAGTGCGACCTTCCCCTCCGAACCCTCGAGTCACTGTTG TCAGGGCTCGGCCCCGCAGGACCTTTTGACATGGTTTACTGGACAGGAGACATACCAGCACACGACGT TTGGCATCAGACTCGGCAGGATCAGCTGCGGGCGCTCACTACTGTTACAGCGTTGGTTCGCAAGTTTC TGGGTCCCGTCCCAGTGTACCCCGCTGTTGGAAACCACGAGAGTACGCCGGTGAACAGTTTCCCCCCT CCGTTTATAGAAGGAAATCACTCCTCTCGGTGGTTGTACGAAGCGATGGCAAAAGCCTGGGAGCCGTG GCTCCCTGCAGAAGCATTGCGGACATTGAGAATTGGCGGGTTTTACGCCCTGTCCCCTTATCCAGGCT TGCGGCTCATATCTTTGAATATGAACTTCTGCTCTCGGGAGAATTTCTGGCTTCTGATCAATTCTACC GACCCTGCAGGACAACTTCAATGGCTTGTAGGCGAACTGCAAGCGGCCGAAGACCGCGGTGACAAGGT GCATATAATCGGCCACATTCCGCCTGGGCACTGCCTTAAAAGTTGGAGTTGGAACTACTACCGGATCG TTGCACGGTATGAAAACACTCTTGCAGCGCAGTTCTTCGGGCATACGCATGTTGACGAGTTCGAAGTA TTTTACGACGAGGAAACTTTGAGTAGACCACTCGCCGTTGCATTCTTGGCGCCGTCAGCTACAACTTA CATAGGTCTGAACCCAGGGTACAGAGTATATCAAATAGACGGGAATTACAGCGGCAGTAGCCATGTAG TCCTGGACCACGAAACATATATACTCAACCTTACCCAGGCAAACATTCCGGGCGCGATTCCTCACTGG CAACTGCTGTACCGCGCACGGGAAACTTATGGTCTCCCCAACACACTTCCGACAGCCTGGCATAACCT CGTGTACCGCATGAGAGGGGACATGCAGCTTTTCCAGACATTTTGGTTTCTGTACCATAAGGGGCACC CCCCTTCTGAGCCTTGCGGTACACCCTGCCGCTTGGCCACCCTTTGTGCTCAACTCTCCGCACGGGCG GATAGCCCTGCATTGTGTAGGCATTTGATGCCAGATGGGAGCTTGCCTGAAGCCCAAAGTCTGTGGCC ACGGCCCCTGTTCTGTGATTACAAGGATGATGACGATAAGTA

The HEXB protein sequence is:

(SEQ ID NO: 16) MELCGLGLPRPPMLLALLLATLLAAMLALLTQVA LVVQVAEAARAPSVSAKPGPALWPLPLSVKMTPN LLHLAPENFYISHSPNSTAGPSCTLLEEAFRRYH GYIFGFYKWHHEPAEFQAKTQVQQLLVSITLOSE CDAFPNISSDESYTLLVKEPVAVLKANRVWGALR GLETFSQLVYQDSYGTFTINESTIIDSPRFSHRG ILIDTSRHYLPVKIILKTLDAMAFNKFNVLHWHI VDDQSFPYQSITFPELSNKGSYSLSHVYTPNDVR MVIEYARLRGIRVLPEFDTPGHTLSWGKGQKDLL TPCYSRQNKLDSFGPINPTLNTTYSFLTTFFKEI SEVFPDQFIHLGGDEVEFKCWESNPKIQDFMRQK GFGTDFKKLESFYIQKVLDIIATINKGSIVWQEV FDDKAKLAPGTIVEVWKDSAYPEELSRVTASGFP VILSAPWYLDLISYGQDWRKYYKVEPLDFGGTQK QKQLFIGGEACLWGEYVDATNLTPRLWPRASAVG ERLWSSKDVRDMDDAYDRLTRHRCRMVERGIAAQ PLYAGYCNHENMDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for HEXB and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

HEXB DNA

(SEQ ID NO: 17) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG  AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA  CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG  TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA  CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG GGAATGAAGTCCTCAAGAACCTGCCTGTCC AAGGATTCCTAAGGAAGCTGTTTATCCCGCTGTTTATCCCCAGAGGGTAAACTGTGTGGCTGGTTGCA GTATCTGTTCCAGACACATAACAGCCAGTCCCAAAAGCGCAGCTGAAACTCTGTTTCCTTTAACCATT CAGACATTTTTAAATGCATATTCTAAGAATTATTAATAAATGCAAATGAATGATTTGCCACAGATTCA TGGGCTAAAATACTAACCTGCACCTCCCCAACCAGATGTGAGCCCCACTATAAGACTGCACAGAAAAC CACAAAGGCAGGGGCATGACACATATACCTCATACCATTAGGTGATGCAACTAGTTTTCTTTCCTTTT TGGAATATAATTTTTTATGATGAGTAAACATGGCTGAGTGGAAGAAAGGAAGCAACAAAGTCCTAGAG CTCCAGTGTTAGGAAGACTTTACAAAGCACCCAGTAATTTCCACAGTGACTTGAGATATAAAAAATGG TGAGGAGCCAGCTTCACTCCCACCTCAAGCTAAGCATCTACTGTCTACTCCATTCTAACCAATGCCCA GTGTTTTGGAGAATGACCATATGAACCTATGGGAATGCATCAGGTTTCCAAAGGGTTAAAACATTCAT TAGCATTCTCAATGCTCCACCACTGTAGTTGCTATTTTAATTAGTACATTCAATCTGGAGTATCTGGA GGAAGACTTTAAACCTAAACCTCAATAGACTGTCTACTTACTCTTGTGAATCTGCCGCCTCTCTCAGA GCAAATGCTGCCCTGAGTGAAGGAAGAATGAGGCTCCCTGAAACTAGGTGCACAGGCACCAAAATGCT TACACATTGAGCTGGAATCATGCTAGGCCCAGAACACATTTCCTTGAACATTAAATTCAGGATGGTGC AAAACAACATTCACAACCAGACTTACACCTAAGAAAACAATTTGCTTAGAAGACCTTAGGATATAGGA TCTACATCTCTCCGCATCCTGTGTTTATGCTCCTGTATGTTCCAGGTTGGCCCAACAAGCCAGAAGGA AGAGCCTAGCCTGTCATCTTGGATACCACCCAGATGGAAAAGCACGTCACAGTCAAAATCACAATCAA CATTCTTGCAACAATGTTTGATTAAAATAAAAAGTAAACTTGGAAACCCAAGAGGAAATACTTGCTTT CTGGTTTAAAACTGTGCAAACCTCAAAATATCAGCAGAAACCATGTATACAAGTCACTGAACACACCT TCAACATAAAATGAATCATCTTTCGAGCATTTTTAAGCCCCCAGAGAAATCACATTTGCATACCAAGT AAGTGGCCAAGAAAATGCACACATGTACTTAACCTACGTCTGCAAAGAAGACAGAGAAAGGGCTGCTA TTACTGTGAACATCAAAAGGGCTTCAGTTACAGTAACTTCAGTTCACTTCATGCTCCTAACTCAGGCT CTCTGCCTCCAATGCTTAGCGTCCCGCACCCTTCTCCAGGTTTTGAACCTGATCTCAATCCAATCAAA AGAGAAACTAAGCAGATTTTTTTCTGGGCATTTACATTACCGGTAACAATAGAACATTATAAAGATCT TGTTAACAAAAGTAGCTTCTTGCCAGAGTCTTTTTATTAACACTTGCAACGCTATTTAACAAGCTGGC CATGCCTGTGTGACACCAAACCGCATGTGGATAAATTCAGTGTTTCATCTCCAGGCCCACCAATTCCT ATCCTTTGTAACTAATAATGTTAACACGACAGATCAAGAAACTAGTTTTTCAGAAAGCAGTTTTCATT CATTCTCTATAGACATTTCCGCCGCAGTGAACATGCCCGCACTCAGGGTGTCTGTGCATGGCCCCAAC TTTCCTCCAAGCCGGGGAGGATGCAACGTGGGCCAACCATCCCGCGCGCTCGGCCCTGGAGGCTGCGG GGAGCGACGCAGCGCGACATTCACCCCCAGGAAAGCGCTGCTTTCCGCAGAGGAGAGAGGCTGAC

ATGGAGCTCTGCGGACTGGGTCTGCCTCGCCCGCCTATG CTTCTCGCGCTTCTGTTGGCCACTCTTCTCGCTGCGATGTTGGCTTTGTTGACACAGGTTGCTCTCGT AGTCCAAGTGGCAGAGGCCGCCAGGGCACCGTCCGTGAGCGCTAAACCCGGGCCCGCTTTGTGGCCGC TGCCTTTGTCTGTTAAAATGACTCCAAATTTGCTCCACCTTGCCCCGGAGAACTTTTACATAAGCCAT TCTCCCAACAGTACCGCAGGGCCGTCATGCACTCTTTTGGAGGAAGCATTCCGCAGATACCATGGATA TATCTTTGGTTTTTACAAGTGGCACCACGAGCCGGCCGAGTTCCAAGCTAAAACCCAAGTGCAGCAAC TGCTCGTATCTATTACACTCCAAAGTGAGTGTGACGCCTTCCCCAATATTAGTAGTGACGAGTCATAT ACCCTCCTCGTTAAGGAGCCCGTTGCTGTTCTGAAAGCTAATCGGGTCTGGGGTGCTCTGCGAGGCTT GGAGACTTTCAGCCAACTGGTGTATCAGGACTCATATGGCACCTTTACGATTAATGAGTCTACGATCA TTGATAGTCCCCGGTTCTCCCACCGCGGTATATTGATTGATACATCCCGGCATTACTTGCCAGTCAAA ATCATTCTGAAAACGCTGGACGCTATGGCGTTTAACAAATTCAACGTTCTTCATTGGCATATAGTAGA CGATCAATCATTCCCTTATCAGAGCATTACCTTTCCAGAACTGTCTAACAAGGGATCTTACTCACTCT CACATGTGTACACGCCTAATGACGTTAGAATGGTGATTGAATACGCGCGATTGAGGGGTATTAGAGTT CTCCCGGAGTTCGACACACCTGGCCATACTCTCAGCTGGGGCAAGGGTCAAAAGGACTTGCTTACACC TTGTTATTCCAGACAGAATAAACTTGATTCATTCGGTCCCATTAACCCTACGCTGAATACTACATATA GTTTCCTTACTACGTTCTTTAAGGAGATAAGTGAGGTTTTTCCCGACCAATTCATTCATTTGGGAGGT GACGAGGTGGAATTTAAGTGCTGGGAAAGCAATCCAAAGATTCAAGACTTTATGCGGCAGAAGGGTTT TGGCACCGACTTTAAGAAACTTGAATCCTTTTACATTCAGAAAGTTCTGGACATAATCGCCACAATTA ACAAGGGTAGTATCGTGTGGCAGGAGGTATTCGATGACAAAGCTAAACTGGCCCCGGGAACTATCGTA GAAGTCTGGAAGGATTCCGCTTACCCGGAGGAACTGAGCCGCGTCACAGCGAGTGGCTTTCCTGTGAT ATTGTCAGCACCTTGGTATCTGGACCTTATCTCCTATGGGCAAGACTGGCGCAAATATTATAAGGTTG AACCTCTGGATTTTGGCGGGACTCAAAAACAAAAACAACTCTTCATCGGTGGCGAAGCCTGTCTGTGG GGTGAATACGTAGACGCTACGAATCTCACTCCCAGACTCTGGCCACGAGCCTCTGCTGTCGGGGAACG ACTGTGGTCTTCAAAAGATGTAAGGGATATGGACGACGCCTATGACCGGCTGACTAGACACAGATGTA GAATGGTAGAGAGGGGAATTGCTGCACAGCCGCTTTACGCCGGGTATTGCAATCATGAGAACATGGAT TACAAAGACGATGACGACAAATA

The SGSH protein sequence is:

(SEQ ID NO: 18) MSCPVPACCALLLVLGLCRARPRNALLLLADDGG FESGAYNNSAIATPHLDALARRSLLFRNAFTSVS SCSPSRASLLTGLPQHQNGMYGLHQDVHHFNSFD KVRSLPLLLSQAGVRTGIIGKKHVGPETVYPFDF AYTEENGSVLQVGRNITRIKLLVRKFLQTQDDRP FFLYVAFHDPHRCGHSQPQYGTFCEKFGNGESGM GRIPDWTPQAYDPLDVLVPYFVPNTPAARADLAA QYTTVGRMDQGVGLVLQELRDAGVLNDTLVIFTS DNGIPFPSGRTNLYWPGTAEPLLVSSPEHPKRWG QVSEAYVSLLDLTPTILDWFSIPYPSYAIFGSKT IHLTGRSLLPALEAEPLWATVFGSQSHHEVTMSY PMRSVQHRHFRLVHNLNFKMPFPIDQDFYVSPTF QDLLNRTTAGQPTGWYKDLRHYYYRARWELYDRS RDPHETQNLATDPRFAQLLEMLRDQLAKWQWETH DPWVCAPDGVLEEKLSPQCOPLHNELDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SGSH and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

SGSH-DNA

(SEQ ID NO: 19) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG  AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA  CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG  TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA  CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT  GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG CACAGTCTCGGCTCACTGCAAGCTCCGCCT CCCGGGTTCACGCCATTCTCCTGCCTCAGCCTCCCAGGTAGCTGGGACTACAGGCACCCGCCACCACA CCTGGCTAATTTTTTGTATTTTTAGTAGAGACGGGGTTTCACCCTGTTAGCCAGGATGGTCTCCATCT CCTGACCTTGCGATCCGCCTGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCTTGAGCCACCGCACC CAGCCTAATTTTTGTATTTTTAGTGGAGACGGGGTTTCACCATTTTGGTCGGGCTGGTCTTGAACTCC TGAGGCCTCCATGAGTCATCTCGCTGGCCCCTCCATAACCAGCTCAGTGTCTGTGTGTGCCAAACAGG CATAGGAGCCTGGGTCGGCCCAGAGACAATCTGCGTCACACACTGTAAACCAAAGGTTCCTTGGGGCC CAGGGGCTGGAAACCTGGAATCGCTGATGGTGTCTGGGATTGATACTGTGTATTCTGCACTGTTTCTG AGATATGGCTGGCAGCAGGGTCAGACGCCTCACCTGGGGCGGGAGTCCAGCCACTTCAGCATAGGCCA GCGCCTGGGGAATGGCAGTGAGGCCAACTGAGAGGCCGGCGACGAAATCCATCTTCAGCCACTGCAGG GAGTAGCTGGGCAGCCACGCCAGGATGGGCAGCCTCCTCTGCAGGGCCGCAGGGGAGCAGCAGCAGGC GCTCGGGGCCATCCCGGGGCCAGAGGACCTGGCCTGACCCAGCGCCGTCACCGAAGAAGGCATCTCTA CGGTGGGGCTGGGGGGTGCAGGTGACACAGACCAGCAGTCAGAGCGTGGCCTTTGAAGAACCCGGCAA CACTGGTCAGGGTCGGCGGGTGTCAGGAGAGGTCACTATGGGTCTCCCCTCCCCAGGGGGGCGAACGG CTCTAAGAGGAAGCCAACAATGTGTGCAAGATGGGGACTGGGCCAAGACTGGAAGGCCCACCCCGTCC CTCATCACCCTCTCTCCCTGAATCCCCCCCGTGCAAATCCTGGGTGCCTTCTGTCCCTCCATCCTCAA CTCTCCCAGATAAGAAACTGATAAGCGATTCCTCATTGAGAAGTCTGAAGACTAATTAGGCTCAACAC TTCTGGCCCCTGGAGAACCGACTTCCTTTGCCTTTTTTTCCGTCTCCCCAGGGAATTTAACGGGGAGC AGCGCAGAGAGAAGCTGGGCCCGCGGGCGCACCGTAGGCTGGCGGGGGGTGCGGGTGGCAGCCAGGAG ATCCAGCGGGGCTCCGAGGTTTTCCAACTGCGCACCAAGGCGGGCTCCACCCGCTACGGTGGACTGCG GCGCTCGAGGGAGAGTGGGGGGGTCCTCCGCTCCTGAGGCCACGCCTCGCTCAGCCCCCACCTGTGGC TTTCACAGCCCTGGAGTTCTAGTTGCTTCTGGGAGGACATCAGAGGCGCCCGGTTAATTCAGGTGCGC AGCATCTTCCAGGGCCCCGGCGCCCGCGCGCAGAGCCGCCACCCTCACCCCCAGCCCCCCACGCCCCC GGCCGCTCCGCTCCGGGCAAAATCCACTCCCCGGCCCCCGGCCCCGCCCACAAGGCCGCTGGCTCCGG ATCCTGGGGTCTCCGGAGGAGACCCTGCGCCACCTGACCGTCCGCGGTCCCTTGGCCCCGAGCAAGGC CGAGGGCCGCGGGGACCCGGGTAGGGACGCGGCGGGGGAGTGGTCCCCACGGGAGGCCCCCGCACTTC AGGACTCCGCGCTGGCCCCCGCGTCGGCTGCCCCCGGCGACCCCGGCCACTGTCCGCTCCCCCTGCCC CTGGTCCCCGCTCGCCGCCCTCGCGGGCCACGGACTCACCCACTCGGCGATGCAGCTTGGGGTCTCCT GGCGTCGCCGCAGCTGGGTCCGCAGGAATCGCCGGGGACAGGCCGGGGCGGGGTCTGGCGCGCACGTG ACCGGGGTCGGGGCAGGGGGCGGGGCCGAGCGGGAGACCAGAGAGCCGGAGCCGGATCCCGATCC

ATGTCTTGCCCGGTACCGGCCTGCTGTGCTCTCCTTCTG GTCCTCGGTCTGTGTCGCGCTCGCCCCCGAAATGCGTTGCTCTTGCTGGCCGACGACGGGGGCTTTGA AAGCGGTGCGTATAACAATAGTGCTATCGCAACCCCTCACCTTGATGCACTCGCACGCCGGTCTCTCC TGTTCAGGAACGCCTTTACATCCGTCAGTTCTTGTTCACCTAGTAGGGCTAGTCTCTTGACAGGCCTC CCCCAGCACCAAAACGGGATGTACGGACTGCATCAAGACGTGCATCATTTCAACAGTTTCGACAAAGT TAGATCCTTGCCCCTCTTGCTTAGCCAGGCGGGTGTGAGGACCGGCATAATTGGAAAAAAACATGTGG GGCCTGAGACTGTCTACCCTTTCGACTTCGCTTACACGGAGGAAAATGGTTCAGTCCTGCAAGTAGGG AGAAACATTACCAGAATTAAATTGCTTGTGAGAAAATTCCTGCAAACCCAAGATGATCGCCCATTTTT TCTGTATGTCGCCTTTCATGACCCTCACCGCTGTGGTCACAGTCAGCCTCAATACGGTACATTCTGTG AAAAGTTTGGCAACGGGGAAAGTGGCATGGGCCGGATTCCTGATTGGACACCACAAGCGTATGATCCA CTGGACGTCCTTGTCCCGTATTTTGTTCCAAACACCCCGGCTGCTCGGGCAGATTTGGCAGCACAATA TACTACTGTCGGGCGAATGGATCAGGGAGTTGGTCTCGTTCTGCAAGAGCTGCGGGACGCAGGTGTCC TGAACGATACGCTGGTAATCTTTACCTCAGACAATGGTATCCCGTTCCCATCAGGGAGGACGAACCTT TACTGGCCTGGTACTGCAGAGCCTCTGTTGGTGTCCTCCCCAGAACATCCCAAGAGGTGGGGCCAGGT GTCCGAAGCTTATGTTTCTCTTCTTGACCTTACCCCGACCATACTTGATTGGTTTTCCATCCCCTATC CGTCTTATGCAATATTTGGTTCTAAAACGATACATCTTACCGGCCGATCTCTTCTGCCGGCGTTGGAG GCGGAACCCCTGTGGGCCACTGTATTTGGTTCACAAAGTCACCATGAAGTCACGATGAGTTACCCGAT GCGAAGTGTCCAGCACAGGCACTTCCGACTCGTGCATAATTTGAATTTCAAGATGCCGTTTCCAATCG ACCAGGATTTTTACGTAAGCCCGACTTTCCAAGACCTGCTGAACCGCACAACAGCGGGTCAACCAACG GGGTGGTACAAAGATTTGCGCCACTACTATTATCGAGCTCGATGGGAGCTGTACGATCGGAGTCGAGA TCCTCATGAAACTCAAAATCTGGCGACAGATCCTAGATTTGCGCAGCTCCTGGAGATGCTTCGGGATC AGCTTGCGAAATGGCAATGGGAAACCCATGATCCTTGGGTGTGTGCGCCAGATGGTGTACTCGAGGAG AAACTGTCCCCGCAATGTCAGCCCCTGCACAATGAGCTTGATTACAAGGACGACGACGACAAGTA

The HEXA protein sequence is:

(SEQ ID NO: 20) MTSSRLWFSLLLAAAFAGRATALWPWPQNFQTSD QRYVLYPNNFQFQYDVSSAAQPGCSVLDEAFQRY RDLLFGSGSWPRPYLTGKRHTLEKNVLVVSVVTP GCNQLPTLESVENYTLTINDDQCLLLSETVWGAL RGLETFSQLVWKSAEGTFFINKTEIEDFPRFPHR GLLLDTSRHYLPLSSILDTLDVMAYNKLNVFHWH LVDDPSFPYESFTFPELMRKGSYNPVTHIYTAQD VKEVIEYARLRGIRVLAEFDTPGHTLSWGPGIPG LLTPCYSGSEPSGTFGPVNPSLNNTYEFMSTFFL EVSSVFPDFYLHLGGDEVDFTCWKSNPEIQDFMR KKGFGEDFKQLESFYIQTLLDIVSSYGKGYVVWQ EVFDNKVKIQPDTIIQVWREDIPVNYMKELELVT KAGFRALLSAPWYLNRISYGPDWKDFYIVEPLAF EGTPEQKALVIGGEACMWGEYVDNTNLVPRLWPR AGAVAERLWSNKLTSDLTFAYERLSHFRCELLRR GVQAQPLNVGFCEQEFEQTDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for HEXA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

HEXA-DNA

(SEQ ID NO: 21) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG  AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA  CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG  TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA  CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT  GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG CCATCTCAAAAAAGAAAAAAATAAAGAGAG ATGGGATTTCCTCGTATTACCCATGCTGATCTTGAACTCCTGGGCTCAAGTGATCCTCCCATCTTGGC CTTCCACAGTGCTGGAATTGCAGGTGTGAGCCACCATCCCCAGCCTGTGATCCATTTTTAATTAAGTT TGTGTATGCTGTGAGGTAGGGGATCATAGTTCATTTTTCCCACATAGGGATATCTATTTTCTTCATCA CCTTTTATTGAAAATAACTTGCCTTCCCCACTAAATTAAATTGGTGTCTTCATTGAAATGGAGTAATA ATCAAATGGCTCTTTTCCTGGACCCTCTATTCCGTTCCATCTATTTGTCTGCCATTATGCCAAAACCC CACTCTAGTGTATAGTAAGGGGGGATATTTTGGAAGATCAACAAATTTATCTTGTGTAACTTACTTTT ATGTATGCATAAGAATATTTGGTTTAAAAATCTGGTTAAGTCTAAAAGAGCTCTTTCAGTAATAATTA AATAACTGAATCCCTGTAATCCACCATGCTCAGCCCCATTAGTAATTTTTATAGCGTCTTTATTTGGA TCTAGCTCTTTCATCTTGTGTAACTCTTTTAAGTAAATGACTCCTCCCTTCTGGTACAGGTTGAATAT CCATAAAAGGGTGCCTTGGCATGTGCTCAGTCCTGAAATTCTACTTTGATCTACTGCTCTCATCTTTG AAACTGCTCTAAACACTCCCCCAAATTATTGATCCTGTGGGCCTGATTATGAACTTGGCTCTTCTGAC AATACTTCTCAAATCCTGTACCTTTGGTAACATCTCTCCTGACTGGCAGAGTACCCAGACACTTAATT AATGCTGATGAAAATTAAGATTTAAGCAAAGAAGAAATTGGTGTAAGAATGCAAGCCTTAGGATCTGA AACTTGATGACTGTGGGATCTAATTTCTGCTTCTTTTGCTACAAGCTCTGTTTTTGAATAATCAACTT TCAAAGACAAATTGCTTGATGAATCTCTGTATTGTCAGAATGTTTCTTTGATTTCCCATCAAAGCCAT GTATGTGTAACTAGTAATTAGGTACCTACGACCTGAATATAAATTATCATTATTTCAGTAGCCCTTTA TTTGTTTTTGAGAAAGGGTTTCACTATACTGCCCAGGCTAAACTTGAACTCCTTGGTTCAAGTGATCC TGCCGCCTCAGCCTCCTGAATAGCTGGGAGTAGCTGGGACTACAGGGATGTGTTATCATGCCCAGTGA AAGCCCTTTATTTTTAAAAGTTCATTTTCCTGATCTTTACATGTATTTTAATACTAAAATTAAATTTA AAAATTTTAAAAAGTACCTACTAACCAAATAATGCCACCCAATAACAATAGCATTATTTGTATTATGT TCTGGTAATATAGTGGTGAACAAGGAAGACAGGGTCTCTGATAACTGTGGAATTCTCCTTGATCACTT CTCAAGCCTCTCTTCCGGATACTATTTCTTGGATCTACAGCTGTCTTCCTTCCCCACTTCTGTAGTTC AGTCTCTCATTATTCTCTACCTCCAATAAAAAGGGGCCTCCTAACTGGTTTCTTATGCAACTACTCAA CATGGTATTTCTAAAATGCAGATCTTTCGGGATGATTTTCAATTGCTCAGAGAATAAATTCCTTGACT TTCTACGTAAGGCCCTGCAGGACCAGGCCCCTGTCATTATCTCTGAGCACTCTCCATCTTGCACCCAA AGCCCCAGCAATATCTTACTGCTTTCAGTAAATACACACCGGGCTATGTGGGGTTTTGTCTGGGGAAA GGGGATGTGAGTTGTAACTAAGAGATTTATAGTCAATCTTGAAGGGAAGAGCTCATATTGGAGGCAAT GGAATGCCTCAAGCTGGCTCTGAAAGTACACATTTTTTCCAGTCATAAGTAGATCACATTTGTGTGAT CTTGTGATCCTCTCTCTAGCAGAGCCGTGCAGACTACCTACTTCCGGCCCTTTCTTGCCCCACGAAAT TTCACATCACAACGACTTGTGGTTTTAATCCTCCGTTTTTCTGCTTCTGAAGTTACTTCAGCCTGGCA AGTCCTTTACCTCCCCGTAGGCCTGGCGAGCTGCATCACAACATTCAAGATTCACCCTAGAGCCATCT GGGAAACTTTCTTCTCCAGGTCGCCCTGCGTCCTCGCCTCCCCACCCCGTTCTTCTCGAGTCGGGTGA GCTGTCTAGTTCCATCACGGCCGGCACGGCCGCAGGGGTGGCCGGTTATTTACTGCTCTACTGGGCCC GTGAACAGTCTGGCGAGCCGAGCAGTTGCCGACGCCCGGCACAATCCGCTGCACGTAGCAGGAGCCTC AGGTCCAGGCCGGAAGTGAAAGGGCAGGGTGTGGGTCCTCCTGGGGTCGCAGGCGCAGAGCCGCCTCT GGTCACGTGATTCGCCGATAAGTCACGGGGGCGCCGCTCACCTGACCAGGG

ATGACGTCTAGCAGATTGTGGTTCAGTCTGTTGCTCGCCGCGGCGTTTGCCGG CCGAGCCACCGCATTGTGGCCCTGGCCCCAGAATTTTCAAACTTCCGATCAAAGATACGTCCTCTATC CTAACAATTTCCAATTTCAATATGATGTGAGTTCAGCTGCACAGCCGGGATGTAGCGTCTTGGACGAG GCGTTCCAAAGATACAGAGATCTCTTGTTTGGCTCAGGCTCATGGCCACGGCCGTACCTTACTGGCAA GCGGCATACACTTGAAAAGAACGTGCTCGTCGTAAGTGTAGTAACTCCGGGTTGTAATCAGTTGCCCA CGCTCGAGAGCGTCGAAAACTACACACTCACGATTAACGACGATCAGTGTCTGCTCCTTTCAGAGACC GTATGGGGGGCGCTGAGGGGCCTTGAAACATTCTCACAGCTTGTTTGGAAATCAGCGGAGGGAACGTT TTTTATCAACAAAACGGAAATAGAAGATTTCCCCAGATTTCCACATAGGGGCCTGTTGCTGGACACCA GTCGCCACTACCTTCCACTCTCATCCATACTTGATACCTTGGACGTAATGGCCTATAACAAACTGAAT GTTTTTCACTGGCACCTTGTAGATGATCCATCCTTCCCTTACGAAAGTTTCACTTTTCCCGAGCTCAT GCGGAAGGGCTCCTATAACCCTGTTACACATATATATACAGCTCAAGATGTAAAAGAGGTGATCGAAT ACGCACGCTTGAGGGGGATACGAGTGCTCGCTGAGTTTGACACACCAGGTCACACACTTAGTTGGGGG CCTGGCATTCCTGGGCTTTTGACACCCTGCTATAGCGGATCAGAGCCCTCAGGGACTTTTGGACCTGT GAATCCATCTCTGAATAATACGTACGAATTTATGAGCACATTTTTCCTGGAGGTCAGCTCCGTGTTTC CCGATTTCTATCTGCATCTGGGAGGCGACGAGGTGGATTTTACCTGTTGGAAATCCAACCCCGAAATC CAGGATTTCATGCGGAAGAAGGGCTTCGGTGAAGATTTTAAGCAACTCGAGAGTTTCTACATACAGAC CCTTCTTGATATCGTCTCTAGCTACGGTAAGGGGTATGTTGTATGGCAAGAAGTATTTGACAACAAGG TAAAAATACAGCCCGACACCATAATCCAGGTCTGGAGGGAAGATATCCCGGTTAATTATATGAAGGAG CTCGAGTTGGTTACAAAAGCAGGTTTCCGAGCGCTTCTCTCTGCTCCTTGGTATCTGAACAGGATCAG TTATGGTCCGGATTGGAAGGACTTTTATATAGTTGAGCCATTGGCATTTGAGGGGACACCTGAACAAA AAGCTCTTGTCATCGGAGGGGAAGCCTGTATGTGGGGCGAATACGTAGATAATACGAACCTCGTGCCG CGATTGTGGCCCAGGGCCGGGGCGGTAGCGGAAAGGTTGTGGTCAAACAAACTTACGTCAGATCTCAC CTTTGCCTACGAGCGATTGTCCCATTTCCGCTGCGAATTGCTCAGGCGGGGAGTCCAAGCCCAACCCC TCAATGTAGGTTTCTGCGAGCAGGAGTTCGAACAAACCGATTATAAAGATGACGATGACAAATA

The IDS protein sequence is:

(SEQ ID NO: 22) MPPPRTGRGLLWLGLVLSSVCVALGSETQANSTT DALNVLLIIVDDLRPSLGCYGDKLVRSPNIDQLA SHSLLFQNAFAQQAVCAPSRVSFLTGRRPDTTRL YDFNSYWRVHAGNFSTIPQYFKENGYVTMSVGKV FHPGISSNHTDDSPYSWSFPPYHPSSEKYENTKT CRGPDGELHANLLCPVDVLDVPEGTLPDKQSTEQ AIQLLEKMKTSASPFFLAVGYHKPHIPFRYPKEF QKLYPLENITLAPDPEVPDGLPPVAYNPWMDIRQ REDVQALNISVPYGPIPVDFQRKIRQSYFASVSY LDTQVGRLLSALDDLQLANSTIIAFTSDHGWALG EHGEWAKYSNFDVATHVPLIFYVPGRTASLPEAG EKLFPYLDPFDSASQLMEPGROSMDLVELVSLFP TLAGLAGLQVPPRCPVPSFHVELCREGKNLLKHF RFRDLEEDPYLPGNPRELIAYSQYPRPSDIPQWN SDKPSLKDIKIMGYSIRTIDYRYTVWVGFNPDEF LANFSDIHAGELYFVDSDPLQDHNMYNDSQGGDL FQLLMPDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for IDS and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

IDS-DNA

(SEQ ID NO: 23) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG  AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA  CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG  TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA  CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT  GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG AAATAAGATCACATTCTGAGGTACTGGGTG TTAGGACTCCAACATACAATTTTTGGGGGGAGGACACTAACACCTAAGTCAAAAAGGACCAAAAGACA TACCATACAAAGCAAAGGCCCTCTGCCCTGCACCTTCCCTCTTCTGTTCTCATTTTAAATGTTTCTAC TTTCATTTCTTCTAGTAGATTGTCCCTGTCTTTCTAAATACTATGCTATTTCTATATCAACTTTCTAA TGTTTTCAACTTTAGACATTGCTGACTTCTTCCTATGATAGATGAGATCACTTATCCATTCCTCTTTT TATGTACATATTTTTAACCTTGGATTTTGGAAATTGATCAAACCTATACAAGATTACAGAAAATAGTA TAATAAACCCCAGGTGTTCATCAATGAACTTCATTGGTTATCAACTCATGACAAATTTTGTTTCATCT CTCCCTGCCATTTTCCCTTCTCCTTTTACTATATAGATTTATTGCCATTTTTAAGTTTTCTATTGTTT ACTTTTGTATCTTTAAGTAATATCCCTAAATCTGTATTTCTCTTTCTATGAACTGGGGACAGCGACTA TTGATTTATTATTATTATTATTATTATTTTTTTGCGATAGGCTGGGGCAAAGGAGACAATCCTAAATT GCTAACCCTAAATTAATGTGCCTACATTTCCTGCCATCTCCCTTCCTCCTCCCAGCTTTTTGTCAACT GTTGCTGCAGGCCAGGTTCCCAAGGAAGCTGACTAAGATGTAGAGTAATGTGCAGGAAGTTTCTTAGG GAGTACTCTTAGGATCAACACCTGTAGAAGGGGAGGGGAGGGAAGAAATCAAAATTCAACAGACAGAG AAAGTGGGCAGTCTCAAAAAAGGCTTCAGTTAACCCCACAGGGAGCTCTGAAGCTGAAATGGCCTTTC AGAGATGTCCCAAGTTGGGGTAAGGGGCTGCACCTTTGTACCTTCAAGTTGAATCACTGATGTGGGCT TCCTGAGAACAGGGGTGACCTTGGCTGAGGTACCTATCTTTTTCTAAGACAATTTCTGATGAGGGCTA ACGACAGCTAACAGCTCTCAAGCCAGCTAGGGAAATAAAATTTTTGGTGTTGAAGGGAGATCTGAGCA GTGCACCACAGCACCATCACAGCTGTATTTGTACCTTCCCATTGTCCATTGTTGTTTAGTCATAATTA AGTCATCTGGGCTTTGTTATAGATTGATTCTCAAAGTTGAAAATCAAACTGTGTTTGCAGTATTAGGA CGGTATAATAGTATTCAGTACAGTACAGTGTAGGGCTAGGATTCCATCTCCCCACAATTGCTGCTCTC TCTGTTTGGCGCACCCTTCTTGCAGACCTCAATGCGGCTTGCTCCCTCACTTGCTTCAAAATTTTGTT CAAATGCCACTTCACTAGTGAGGCCCTGCCTGGCCACCCCATAGAAAATAACAAGCATGCCCCGCACC CACGCTTTATTTTTCTCCAGACCGGGTATGCCCACCGACACTCTCTATATTTTTTTATTGTTTTAAGC TCCACCAAAGCAGGGACATAGAGCCCCAGTGCCACCAACAGCGCCTGGTATACATATTTGCGATACTT AATAAGAATTAGTTGAAGAAATGAATAGGAAAGGGAGTCCCTTTAGATGGAGGAAGGGACTTTCTCAA AAGGCCTCATGGAAGGAGAATGGCATTGAGGCTGGCTTACAAGAAGTGTGTCTTTTATAAAAAGAAGG AAGGGCAGGGCTTCCAGGTGAAAGGCATAGCACAAGCAAAGGCAAAAAGACGGGTAACTGCTAGTTGT TAAGGGCAGTGGCTGAATCGCTATACCCCTAGCAGTTCTACACCTAGGGGCCTGCGGGCCGCTGGGTC TGCGAAGCTTGCAAGGCAACTGGCCCGCCCCCGCTCTGCGCCTGTCTCTCGGCCACGCCTATTGCTGC AGGATGACGCGCACCTCTAGAACCCGCCCCGGAGGGGAGGGACGCAGGGAAGAGTCGCACGGACG

ATGCCGCCTCCTCGGACGGGGCGCGGGCTTCTGTGGCTC GGTTTGGTATTGTCTTCAGTGTGCGTGGCCCTGGGATCAGAAACTCAGGCGAACTCCACGACTGATGC ATTGAACGTATTGTTGATAATAGTTGATGACCTGAGACCCAGTCTCGGCTGCTACGGTGATAAACTCG TACGAAGCCCCAACATTGATCAATTGGCAAGTCATTCCCTCTTGTTTCAGAACGCTTTTGCCCAACAG GCGGTTTGCGCACCGAGCAGGGTTTCCTTCCTCACAGGCCGCCGCCCTGACACTACCCGCTTGTACGA CTTTAATTCATACTGGCGCGTCCATGCCGGTAACTTCTCTACGATACCGCAATACTTTAAGGAAAACG GTTATGTCACTATGAGCGTAGGTAAGGTATTTCACCCGGGGATCAGTTCCAACCACACCGACGATTCT CCTTACTCTTGGAGTTTTCCTCCATATCACCCAAGCAGCGAAAAGTATGAGAATACAAAAACTTGTAG AGGCCCCGATGGTGAGCTTCACGCAAATCTGCTTTGCCCAGTCGATGTGCTCGATGTCCCAGAGGGCA CTCTGCCGGATAAGCAATCCACGGAGCAGGCTATACAGCTGCTCGAAAAGATGAAAACTTCAGCGAGC CCGTTTTTCCTCGCGGTGGGTTACCACAAGCCGCATATCCCGTTCCGGTACCCTAAGGAGTTTCAAAA ACTTTATCCGTTGGAGAATATCACACTCGCGCCCGACCCCGAAGTCCCAGATGGACTTCCTCCGGTCG CTTATAATCCCTGGATGGACATTCGCCAGAGGGAAGATGTACAAGCTCTCAATATCTCTGTTCCATAC GGGCCCATTCCGGTTGACTTTCAGAGGAAGATTAGACAATCATACTTCGCCAGCGTATCCTATCTTGA CACCCAAGTTGGACGCCTGCTCTCCGCGCTTGATGACCTGCAACTGGCAAACAGTACCATAATAGCCT TTACCAGTGACCACGGTTGGGCACTCGGAGAACATGGAGAGTGGGCCAAGTATAGTAATTTTGACGTG GCTACCCATGTACCATTGATTTTTTATGTTCCCGGCCGGACAGCTAGTCTCCCGGAGGCTGGAGAGAA ACTGTTTCCATACCTTGACCCCTTTGATTCCGCGTCTCAGCTTATGGAACCGGGCCGCCAAAGCATGG ACTTGGTTGAACTGGTTAGTCTCTTCCCGACGTTGGCTGGCCTTGCAGGGCTCCAAGTTCCACCGCGG TGTCCCGTACCTAGTTTCCACGTTGAACTCTGTCGGGAGGGGAAGAACCTCCTTAAGCACTTCCGCTT TCGGGATCTTGAGGAGGACCCCTACTTGCCAGGTAATCCTAGAGAGCTGATAGCGTACTCCCAGTACC CACGACCGTCTGATATTCCACAGTGGAACTCCGACAAACCTAGTCTGAAAGACATTAAGATCATGGGC TACAGTATTAGAACGATTGACTACAGGTATACCGTGTGGGTCGGCTTTAATCCAGACGAATTTCTCGC GAACTTTAGCGATATCCATGCGGGTGAGCTTTATTTTGTTGATTCCGATCCGCTCCAGGATCATAATA TGTATAATGATTCACAAGGAGGTGATTTGTTTCAACTTCTCATGCCGGACTACAAGGATGATGACGAC AAGTA 

The NEU1 protein sequence is:

(SEQ ID NO: 24) MTGERPSTALPDRRWGPRILGFWGGCRVWVFAAIFLLLSLAASWSKAEND FGLVQPLVTMEQLLWVSGRQIGSVDTFRIPLITATPRGTLLAFAEARKMS SSDEGAKFIALRRSMDQGSTWSPTAFIVNDGDVPDGLNLGAVVSDVETGV VFLFYSLCAHKAGCQVASTMLVWSKDDGVSWSTPRNLSLDIGTEVFAPGP GSGIQKQREPRKGRLIVCGHGTLERDGVFCLLSDDHGASWRYGSGVSGIP YGQPKQENDFNPDECQPYELPDGSVVINARNQNNYHCHCRIVLRSYDACD TLRPRDVTFDPELVDPVVAAGAVVTSSGIVFFSNPAHPEFRVNLTLRWSF SNGTSWRKETVQLWPGPSGYSSLATLEGSMDGEEQAPQLYVLYEKGRNHY TESISVAKISVYGTLDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for NEU1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

NEU1-DNA

(SEQ ID NO: 25) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG ATCATGGTGAGTGACTCCCCTCTCTGCTGC TCCACCCCCAACTCCCCAGAGGAACCCAATAACCCCAACGGGTCATGTCTTCCAGACCTCCATCCTGG GGGCCTATGTCATCGCCAGCGGCTTCTTCAGCGTTTTCGGCATGTGTGTGGACACGCTCTTCCTCTGC TTCCGTGAGTGACACCCCCAGCCACCTGTCCCCAACCTTAAAGTACTGAGCCGTTCAAGCATTTTTTT TTTTTTTTGGAGATTTGGTGCTTCTAGAAAGAATGCCTTTGTGAGCTAAACGAACCAGAGGGAGCTTC TTGTGACATCCTGAGGCCAGGCGTTTAGGGAAGAAGGAAGAGAGTGAGCCCCCAGGCCGGTAGGCTCT CCAAAGAAGGAGCATTCTGATGGAGAGGTCTCTGCTATCTTCCCTAAGAAATCTCGGGTAGAAGTTAG CCATTAGAGGCCAGGCATGGTGGCTCACGCCTGTCATGCCAGCACTTTGGGGGACCGAGGTGGGCAGA TCACCCTGAGGTCAGGAGTTCGAGACCAGCCTGGCCCACATGGTGAAACCCCTCTCTACTAAAAATAC AAAAAATTAGCTGGGCGCGGTGGCGGGCGCCTGTAATCCCAGCCACTTGGGAGGCTGAAGCAGGAGAA TCGCTTGAACTCAGGAGGCGGAGGTTGCAGCGAGCCGAGATTGCGCTACTGCACTTCAGCTTGGGCGA CAGCAAGACTCCGTCTCAAAACAAAGAAAAAAGATTAAAAAAAAAAAAGAGCCATTAGAGAGACTTCC CAGCAGGTGGCTGTAGCGGCAGGGGATTTTCTTACTCTACAGCATGCATCCATTCAGGGTTTGCCAGT CTCCTCCTAAGCGACTGACATGCATTTTTTCCGCTAATTCTTATCATCGCTCTATGCAACATAATATT CCCGACCCCACTTCACAGGAGGAAACTGAGATTACATAACCTGCCCGGGGGTAAGGGTGGTGGTGCAG CTTGGATTCCAAATCCCGCAGGCAGCTTGCCTCCCAGTCCCCGATTTCCTGGCCCCAGGGTCCGCTCT AACCGGTCTCTGTTGCGGCTCAGTGGAAGACCTGGAGCGGAACAACGGCTCCCTGGACCGGCCCTACT ACATGTCCAAGAGCCTTCTAAAGATTCTGGGCAAGAAGAACGAGGCGCCCCCGGACAACAAGAAGAGG AAGAAGTGACAGCTCCGGCCCTGATCCAGGACTGCACCCCACCCCCACCGTCCAGCCATCCAACCTCA CTTCGCCTTACAGGTCTCCATTTTGTGGTAAAAAAAGGTTTTAGGCCAGGCGCCGTGGCTCACGCCTG TAATCCAACACTTTGAGAGGCTGAGGCGGGCGGATCACCTGAGTCAGGAGTTCGAGACCAGCCTGGCC AACATGGTGAAACCTCCGTCTCTATTAAAAATACAAAAATTAGCCGAGAGTGGTGGCATGCACCTGTC ATCCCAGCTACTCGGGAGGCTGAGGCAGGAGAATCGCTTGAACCCGGGAGGCAGAGGTTGCAGTGAGC CGAGATCGCGCCACTGCACTCCAACCTGGGTGACAGACTCTGTCTCCAAAACAAAACAAACAAACAAA AAGATTTTATTAAAGATATTTTGTTAACTCAGTAAATCTGTGACTCATTCTCTCCACGACGACAGGCG GCCTTTTTTTTTCCGCGCCCGGCTCTTTAAAATCGGCCCCGCCCCTGTGACGTGTCCTGGTGCCGCGG CCAATCAAAAAGCCCAATAAGGATGGTGCCAGTCCCTTCTTCACCCCAGCCAGTCCGCTTCCCGTTCG GGTCACGCGCTCCGGGCCTCCAAGAGGGCCTCCAAGAGGGCCAATCGGAAGGGCAAGCTTCGAGATGC TGCGTGATCACGTGGGAGGAGATGAGCTACTTGAAGACCAATTAGAGTCCGGGAAGCGCGGCGGGGCC TCCAGACCGGGGCGGGCTTAAGGGTGACATCTGCGCTTTAAAGGGTCCGGGTCAGCTGACTCCCG

ATGACAGGCGAACGCCCTAGCACTGCATTGCCTGACAGA CGGTGGGGCCCTCGAATACTCGGGTTCTGGGGAGGGTGCAGAGTATGGGTTTTTGCGGCCATATTCCT CCTGTTGAGCCTGGCTGCATCCTGGTCAAAAGCGGAGAACGACTTTGGGCTGGTGCAACCGTTGGTTA CGATGGAGCAGCTCCTGTGGGTTAGCGGCAGACAGATCGGGTCAGTAGATACGTTCCGAATACCACTG ATCACAGCCACTCCGCGAGGCACACTCCTTGCTTTTGCAGAAGCCAGGAAGATGAGCTCATCAGACGA GGGCGCTAAATTCATCGCATTGCGGCGATCCATGGACCAGGGATCTACATGGAGCCCGACGGCATTTA TAGTGAACGATGGGGACGTGCCGGATGGACTTAACCTTGGAGCGGTTGTATCAGATGTGGAGACAGGC GTTGTGTTTTTGTTCTACTCACTTTGCGCACACAAGGCGGGCTGCCAGGTTGCTAGCACTATGCTCGT ATGGTCCAAGGATGACGGCGTGTCCTGGTCTACGCCACGAAATCTCTCACTCGACATTGGTACTGAAG TATTTGCACCAGGGCCGGGTTCCGGTATCCAGAAGCAACGGGAACCTCGGAAAGGTAGACTTATAGTA TGCGGACACGGAACTCTTGAGCGGGACGGCGTTTTCTGTCTCTTGTCTGACGATCACGGGGCATCCTG GAGGTATGGTAGTGGGGTTAGTGGGATACCCTATGGCCAGCCTAAACAGGAGAACGATTTTAATCCGG ACGAGTGCCAGCCTTATGAACTTCCCGACGGCTCAGTGGTCATAAATGCGCGCAATCAAAATAACTAT CACTGCCACTGTAGGATTGTGTTGCGGAGTTACGATGCTTGTGATACACTGCGACCGCGAGATGTGAC ATTCGACCCAGAATTGGTGGACCCCGTAGTAGCGGCGGGGGCCGTGGTCACAAGTTCAGGGATAGTTT TTTTCAGTAACCCTGCTCATCCCGAGTTTAGAGTGAATCTCACTCTTCGGTGGTCTTTTTCCAATGGG ACCAGTTGGAGAAAAGAAACGGTACAACTCTGGCCTGGACCGTCCGGTTATTCTAGTCTCGCGACGTT GGAGGGGTCAATGGACGGAGAGGAGCAGGCCCCGCAACTCTACGTCCTGTACGAGAAGGGGCGGAACC ATTACACCGAGTCAATAAGTGTCGCTAAAATCTCCGTTTACGGCACATTGGATTACAAGGACGACGAT GACAAGTA

The SUMF1 protein sequence is:

(SEQ ID NO: 26) MVPIPAGVFTMGTDDPQIKQDGEAPARRVTIDAFYMDAYEVSNTEFEK FVNSTGYLTEAEKFGDSEVEEGMLSEQVKTNIQQAVAAAPWWLPVKGA NWRHPEGPDSTILHRPDHPVLHVSWNDAVAYCTWAGKRLPTEAEWEYS CRGGLHNRLFPWGNKLQPKGQHYANIWQGEFPVTNTGEDGFQGTAPVD AFPPNGYGLYNIVGNAWEWTSDWWTVHHSVEETLNPKGPPSGKDRVKK GGSYMCHRSYCYRYRCAARSQNTPDSSASNLGFRCAADRLPTMDDYKD DDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SUMF1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

SUMF1-DNA

(SEQ ID NO: 27) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG ATAGCTGGACCAGGAATCAAAGAAGTTCAG GTCTCTGAAGCGCAGCTGACACAGCATGTGCTGAGACTGATATTTGAAGGAGGCGAACAAAGATTACC GTTGACCTAGACCTTGACTATATATTATGCACAGTAAATACATACAACCTTGGTTAAGGCATTGACCT TTTAGCTTCATCAATTTTGAAATGAGTATAGTAATAATACATTTCTTGCCAAGTGGTTGTAATCTCAA ATGAGAAAATGTGTGAAAGGCCTTGGCAAACTGTAAAATAGTCAACAAGGAGAAAAGGCCTTTTTTTT TTTTTTGAGAGATGGTCTCACTTTGTCACCCAGGCTGGAGTGCAGTGGCACAATCATGGCTCACTGCA GCCTCTGCCTACCAGGCTCAAGTGATCCTCCTGCCTCAGCCTCCGAAGTAGCCAGGACCACCGGTGTG CGTCACCATGGCCAGTTAATTTTCTTAATTTTTTGTAGAGACAAGGTCTTGCTGTGTTGCCCAGGCTG GTCTCAAGCTCCTGGCCTCTAGCGATTCTCCTGCCTCGGCCTCCTAAAGTGCTGGGATTACAGGCTTG AGACACGGTGCCTGGCTGGTCTTTTCTTTATGCTAAAAAAATTCAAACAGATGCTACATTAGAATAGT GCAATAAACACCCAGATGCCCATCAACCAGCTATGACAGTTATCAACTCATGGCCAATCATGCTTCAT CTTTAGCCAGACCCTGATTACCCATTTTTTGGGAAGCAAATCTTTGACTGCCTATATTTTTATCCATA TATATATATGTGTGTGTGTGTGTGTGTGTGTGTGTATACCTCAGTGAGTGTGTGTGTACCTCAGTGAG GGGATTCTTTTAAAAAATATAGCCACAAATACCATTATTACTCCTAAAAGCCTAAAAACAAAATTTAC AGCAATTCCTTAATTTTATCAAATATTATAATTTGACTTAGTGGTTAAATTTCCCTGATTATCTCAAA AATTTTGAACTCAGTAGGTTTGAATTAGTATTTAGATAAGGTTCACATATTGCAGCTGGCTGCTATGT TTTTTTTTTTTTTTTTTTTTTCAGATGGAGTCTTGCTCTGTCCCCAGGCTGGAGTGCGGTGGCGCCAT CTCGGCTCACTGCAAGCTCCACCTCCCGGATTCATGCCATTCTCCTGCCTCAGCCTCCCGAGTAGCTG GGACTACAGGCGCGTGCCACCACGCCGGGCTAATTTTTTGTATTTTTTAGTAGAGATGGGGTTTCACC GTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCGTGATCCACCCGCCTCGGCCTCCCAAAGTGCTGG GATTACAGGCTTGAGCCACCGCGCCCGGCCTGCTATGTTGTTTTTTAATCTGTAAGTTTCTCCTTCAT CTTCTTTTTGTTTTGGTTTTGCATTTTGTTCGATTACGGAACTGTAGAACAGTGGTTCTTAAACTTAA GTGTGGATTAGAATCATCTGGAGAGCTTGTGAAACCCTGGATTGCTGTGTCCAGTCCCCACGGATTCT GATTCCGTATTGTATTTCTCTTTTTTTTTTGAGACGGAGTCTTGCTCTGTCGCCGAGGCTGGAGTGCA GTGGCGGGATCTGGGCTCACTGAAACCTCCGCCTCCCAGGTTCAAACGATTCTCCTGCCTTGGCCTCC CGACTAGCTGGGACTACAAGCGCGCCATTACTGGGTCTTTGTGAGGATTAAATGAGATTTTAAAAAGT GAAGTGCTTAGCATAGTACTCTGGCACTTACCAAATGCCCAGCAAATTTGACTGTTATTTTTCAACCA AGAAATCATAAAGGGGTGCACGGTCTGTGGAAGGCCTTGAGTTTTGTGGAGTTTTGTGTTTTGCTGCG TTTTGACGTTAGCACAGGCAAGCAGCAGCGCCAAAGAAGTACCTGAAGAAAGGTGAAGAGCAACTCTC CTGGTCACTTCGTAAGTCAGCTCAAAATTCTGCCCCTTTAAGGAGGGCTCAG

ATGGTTCCAATCCCCGCCGGGGTGTTCACCATGGGGACGGACGACCCACAGAT TAAGCAGGATGGCGAAGCTCCAGCGAGAAGAGTCACCATAGACGCTTTTTACATGGATGCTTACGAAG TGTCTAACACGGAGTTTGAAAAATTTGTTAATAGCACAGGTTATTTGACGGAGGCGGAGAAGTTCGGT GACAGCTTTGTCTTCGAGGGCATGCTTTCTGAACAGGTGAAGACTAACATTCAGCAGGCAGTTGCAGC GGCACCTTGGTGGCTCCCAGTTAAGGGGGCAAATTGGCGACACCCAGAGGGACCAGACTCTACTATAT TGCACCGGCCTGACCACCCGGTTCTTCACGTATCCTGGAATGACGCCGTTGCCTACTGCACCTGGGCA GGAAAACGACTGCCGACCGAAGCAGAGTGGGAGTATTCTTGTAGAGGAGGACTGCATAATCGGCTTTT TCCCTGGGGTAACAAGCTTCAGCCCAAAGGCCAACACTATGCTAACATCTGGCAAGGGGAATTTCCCG TCACGAACACTGGGGAGGACGGATTTCAGGGGACCGCACCTGTAGATGCGTTTCCCCCCAACGGGTAT GGTCTCTACAACATCGTCGGTAATGCCTGGGAATGGACCAGCGACTGGTGGACGGTGCACCATTCTGT TGAAGAAACATTGAATCCCAAAGGGCCACCAAGCGGAAAGGATCGAGTGAAGAAAGGCGGATCTTATA TGTGTCATCGGTCCTACTGCTACCGGTATCGGTGTGCTGCTCGCTCTCAGAATACACCCGACTCAAGC GCAAGCAATCTTGGTTTCCGGTGTGCGGCCGATCGCTTGCCGACAATGGATGACTACAAGGACGATGA CGACAAATA

The GAT1 protein sequence is:

(SEQ ID NO: 28) MATNGSKVADGQISTEVSEAPVANDKPKTLVVKVQKKAADLPDRDTWKG RFDFLMSCVGYAIGLGNVWRFPYLCGKNGGGAFLIPYFLTLIFAGVPLF LLECSLGQYTSIGGLGVWKLAPMFKGVGLAAAVLSFWLNIYYIVIISWA IYYLYNSFTTTLPWKQCDNPWNTDRCFSNYSMVNTTNMTSAVVEFWERN MHQMTDGLDKPGQIRWPLAITLAIAWILVYFCIWKGVGWTGKVVYFSAT YPYIMLIILFFRGVTLPGAKEGILFYITPNFRKLSDSEVWLDAATQIFF SYGLGLGSLIALGSYNSFHNNVYRDSIIVCCINSCTSMFAGFVIFSIVG FMAHVTKRSIADVAASGPGLAFLAYPEAVTQLPISPLWAILFFSMLLML GIDSQFCTVEGFITALVDEYPRLLRNRRELFIAAVCIISYLIGLSNITQ GGIYVFKLFDYYSASGMSLLFLVFFECVSISWFYGVNRFYDNIQEMVGS RPCIWWKLCWSFFTPIIVAGVFIFSAVQMTPLTMGNYVFPKWGQGVGWL MALSSMVLIPGYMAYMFLTLKGSLKQRIQVMVQPSEDIVRPENGPEQPQ AGSSTSKEAYIDYKDDDDK 

GAT1 DNA

(SEQ ID NO: 29) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG AGGTCGGGTCTGCTCAAGTTCTGCAAAGAT GGCTGCCAACACCTCTATGCTTAGGAGCTTTGGTGGAGATTGAGTTTCTGTTTGACAATAGTTTTAGC AAAAGTCCCAGACAGAGTTCTCATTGGCCCAGCATATGTCACACGTCCCCTCATTGAGGTCAGAGTGA TGTGCTCTGATTATCTGTGCCCTGGGTCACATGTCTGTCTCCAGGAGGAGGGAGCCCCACCCAACCAT ATTGAATATGAGTGAAGGAGGGGAAGTTTCCCAAATGAAAATTGAGGTTCTGTCACCCAAAGAAGTTG AAATGAATGTCAGGCAAGCAAAAGTAGCCTTCATTTTTGCTACCCTTGTATCTCCACTCAAAGCTATG CCCCACATCTCCATCCAGACAGCTCCTACTCATCCTTCAGACCTCAGTTCAAATGGCGCTTCCTTGAG GAAACCTTCCCAAACCATCCCACACTAGACTGGAATCCCCTGCTGGACTAGAATCCCCTGCATGTGTG CTCCTGGCAGAGCTTGTCATTCTGGGTTTGTGCGGTTATTTGATGAAAGCCTGTCTCCCATACTGGAC TGGCATCACCTTGAAAGCTGTGGCCTGTCTTGTCCATCGCTCTGTCCCTGGAGCCTAGGACAGTGCCT GGCACACAGGTGGAACTCGGGAAATATTTATTTGAAATACCAACGGAAGTCCACAGCACATATGACCT GGTGATCAGTGGTGGGAGGTGAATGGGTCAAGAAAGACACCAAGATTCCCTGCTCATGAGTGAGAGTG TGGGGAAACAGAAGAAGTCAGGGTGACCTTGGTGAGCACTGCCCTGGGGGACTCGAGGATGGATGAAA GCAGGGAGGAGGCCAGATTAGGTGGGGTAGAGGACCTGAGGTCCATCAGCAAAGGCCATCCCTGGGGA CAAAGAGAGGAGGGGAAGAGTAGGTCTGGGCTGGAGAGAAGGAATCTTTTCTCTGAGTTCCTGGGGAC CCCAGAGGGAAGGGCAGATGTGGCCCCATTCCCAGAAGCCTTTATAAAAGAGGGTGGGGAGGTCAGGC CTTGGCAAGGACAAGGGAAGGAGTCCCTACGTGCTGGATTGGGATTGGCTGGAAAGGGGACTTCTCTG GGAGAATCCCTCAAACCTCAAGAACTGAGAGAAGGGTGTCTGGGGCTCCTGCCACCATCCCTGTTTCC CTTTTAAGTAATCTGTTTCCCCATCTGTCCATCCATACACACAGCCACTTGTGTCTCCATGACCAACC GCTGGCAGTGGAAGGGTGTCCTTCCCACCCCCACTCTTACACACACTCCCAGCTGGTACCCAGAGCCT GGTCACCCCAGGCCAGGCCTGTGTTTCCAGGTGTAACGGGCAGCAGACGCTGCCCTAGGACTAGAGCA GGGAGGGGGCACGGGCCCACCCCAACCCACAGCGACCCACAGAGGGCGAAAAGAGGACGACCGCAGAG AGAAACGGAAAGGACAGGCCAACGGAAGCAGTACTGCAAGGCTGGAAGGAGAAAAGCCAGGAGGGGAG TGCTTGCTGTGAAAGACAGGGAGACAGAGACCAAGACGGACAGGCAGACAGGCTGGTGACCCAGGATG AGGCCGGAAAGAGCCATCAAAGGAAGGAGAAGGAAGGAGAGAGATTGGAGCGGGACGGCGGGGCAGGC GAGGGAAGGAGGGGGTGGGGAGAGGGAGGGAGGAAGAGAGGGGAGAAAGAGGGAGGAAGAGAGGGGAG AAGGAGGGAGAAGAGAGCGGGAGAATGCGAGAGGAAAGAAGGGAGAGGGGAGGCGTAGAAGGGGAGAG GAGGTGAAGGGAAAAGGAGAGAGCCTGCTGGCGGCGAAGCTGCAAGAGGCAGCTGCGGAGGGAGCGCG CGGCGGGCCTGGGGGAGCGCTGGGCGGGGGCGGGCGGTGCGGGCAGGGCTATACCCGAGCTGGGCGGG CTCCGGGCGCCGCGGGCCCTGCCCTCCCCCTCCATCCCTCCGGACTCGCTCCCCCCTCCTCTCCCTTC CCCGCGACCCTCCGCC

ATGGCAACTAACGGTAGTAA AGTCGCGGACGGTCAGATCTCCACAGAAGTTTCTGAAGCGCCGGTCGCAAATGATAAACCAAAGACCC TCGTAGTCAAGGTACAGAAAAAAGCTGCTGACCTTCCTGATCGAGATACCTGGAAGGGCAGGTTTGAT TTCCTCATGTCATGCGTTGGGTACGCCATCGGCCTCGGAAACGTATGGAGGTTCCCCTACCTGTGCGG TAAGAATGGTGGCGGAGCCTTCCTGATACCATACTTTTTGACTCTCATATTCGCAGGCGTGCCACTCT TCTTGCTCGAGTGCAGCTTGGGCCAGTACACGTCTATAGGCGGCTTGGGCGTATGGAAGCTGGCGCCC ATGTTCAAAGGTGTTGGCTTGGCCGCTGCTGTACTGTCCTTTTGGCTGAACATTTATTACATAGTGAT CATATCCTGGGCAATTTACTACCTCTACAATTCTTTTACGACAACACTGCCCTGGAAGCAATGCGATA ACCCATGGAATACGGACCGATGCTTTTCCAACTATTCAATGGTAAACACCACGAATATGACGTCTGCG GTAGTCGAATTTTGGGAACGGAACATGCACCAGATGACCGATGGTCTCGATAAACCGGGTCAGATTAG ATGGCCACTCGCAATAACTCTTGCCATCGCATGGATACTCGTATACTTTTGCATCTGGAAAGGTGTCG GATGGACAGGCAAAGTAGTCTATTTTAGTGCTACATACCCTTATATCATGTTGATTATACTGTTTTTC AGAGGAGTCACACTTCCTGGGGCGAAGGAGGGCATTCTCTTCTATATCACGCCAAACTTTCGAAAGCT GAGTGACTCAGAGGTTTGGCTCGATGCTGCAACTCAGATATTCTTCTCATACGGCCTTGGTCTGGGTA GTCTCATAGCCTTGGGTTCCTACAATTCCTTTCACAATAACGTGTACCGAGACAGCATTATAGTATGT TGTATTAATTCTTGCACTTCAATGTTCGCCGGTTTCGTCATTTTCAGCATTGTCGGATTTATGGCGCA TGTTACCAAAAGGAGCATTGCGGATGTGGCGGCTAGTGGGCCAGGACTCGCTTTCCTCGCCTACCCAG AAGCAGTTACTCAGTTGCCGATTAGCCCACTGTGGGCTATCTTGTTCTTTTCTATGCTCCTTATGCTT GGGATAGATTCCCAGTTTTGCACGGTAGAGGGTTTCATAACGGCACTTGTCGATGAATATCCGCGACT CCTGAGAAATAGACGCGAACTCTTTATAGCAGCGGTATGTATAATCTCATATTTGATAGGCTTGTCAA ACATAACACAAGGGGGAATATACGTTTTCAAATTGTTCGACTACTATAGTGCCTCCGGGATGTCACTT CTTTTCCTGGTATTTTTCGAGTGCGTTTCAATCAGTTGGTTTTATGGCGTGAATCGATTTTATGACAA CATTCAGGAGATGGTAGGAAGTAGACCGTGCATATGGTGGAAACTCTGTTGGTCTTTTTTCACGCCCA TCATCGTGGCCGGCGTGTTTATATTTAGCGCAGTGCAAATGACTCCTCTCACTATGGGGAACTATGTC TTCCCCAAATGGGGCCAAGGGGTAGGCTGGCTCATGGCGTTGAGTTCCATGGTCCTTATTCCAGGTTA TATGGCTTACATGTTCCTGACACTGAAAGGGAGTCTGAAACAACGGATTCAGGTGATGGTTCAACCTA GTGAAGATATTGTCAGACCTGAGAACGGTCCCGAGCAACCTCAGGCGGGAAGTAGTACCTCTAAGGAG GCTTATATAGACTATAAAGACGACGACGATAAATA

The FIG. 4 protein sequence is:

(SEQ ID NO: 30) MPTAAAPIISSVQKLVLYETRARYFLVGSNNAETKYRVLKIDRTEPKDLVII DDRHVYTQQEVRELLGRLDLGNRTKMGQKGSSGLFRAVSAFGVVGFVRFLEG YYIVLITKRRKMADIGGHAIYKVEDTNMIYIPNDSVRVTHPDEARYLRIFQN VDLSSNFYFSYSYDLSHSLQYNLTVLRMPLEMLKSEMTQNRQESFDIEEDEG LITQGGSGVFGICSEPYMKYVWNGELLDIIKSTVHRDWLLYIIHGFCGQSKL LIYGRPVYVTLIARRSSKFAGTRFLKRGANCEGDVANEVETEQILCDASVMS FTAGSYSSYVQVRGSVPLYWSQDISTMMPKPPITLDQADPFAHVAALHFDQM FQRFGSPIIILNLVKEREKRKHERILSEELVAAVTYLNQFLPPEHTIVYIPW DMAKYTKSKLCNVLDRLNVIAESVVKKTGFFVNRPDSYCSILRPDEKWNELG GCVIPTGRLQTGILRTNCVDCLDRTNTAQFMVGKCALAYQLYSLGLIDKPNL QFDTDAVRLFEELYEDHGDTLSLQYGGSQLVHRVKTYRKIAPWTQHSKDIMQ TLSRYYSNAFSDADRQDSINLFLGVFHPTEGKPHLWELPTDFYLHHKNTMRL LPTRRSYTYWWTPEVIKHLPLPYDEVICAVNLKKLIVKKFHKYEEEIDIHNE FFRPYELSSFDDTFCLAMTSSARDFMPKTVGIDPSPFTVRKPDETGKSVLGN KSNREEAVLQRKTAASAPPPPSEEAVSSSSEDDSGTDREEEGSVSQRSTPVK MTDAGDSAKVTENVVQPMKELYGINLSDGLSEEDFSIYSRFVQLGQSQHKQD KNSQQPCSRCSDGVIKLTPISAFSQDNIYEVQPPRVDRKSTEIFQAHIQASQ GIMQPLGKEDSSMYREYIRNRYLDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for FIG. 4 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

FIG. 4-DNA Sequence

(SEQ ID NO: 31) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG GTAGCAGCTGCTATTAGTGCCTCCCCCATA TCCACTTGACATACACCTTTTCTATGCACGACCAGCCCAACTTCCAAAATGTTAGCATGTGCGACTTT TTGCCTAAGGGCTTTCTCTGGCTGCCAGAACCTACTCTCCCTGAACACAGGGTAGACTGGAAGTTCTA GGGCATCAATGTTCTGCCCTATCAGGCTTCATCCAATAACTGATGGAAGTTGGCGAATAAATACTCCA GCTTCCTTGCCCCTCAAGAGGGGATAACTGAGACATGCCTCCCAGTATTCCCTAGTGAATTCAGCCCA CAGAGAAATTTCTCTGGTAATATTTCCTTTATTAGTTTTCTTCCCCTCCCTGCTGCTGTTTCCTGGGA TTACGTCTCATATAAACAACCTGCCTTCAAAGTTTTGTCTTAGGATCTGATTCCGGGTGAAATAAACT AAGATAAAGTTAAAATGGAAGTGCTAAACTATAATAATTGAAAACTAGAATCCTTCAGGTATTTTAAG AGTTGCTATCCTAGATAAAAACACTGTGCAAACATTTAACTAATATTCAGAAGAGTTGGTTTCATTAT GAAACAGAACACAGCTAACTATTTTTCCCAGTTAAAAGATCCAAGTCCAAAATGCCAGAACGGACACG GCCATCCTTCTAGTTCTTAATAAAAGGAGTACCAAACTACAGGGGGAAAGAAGCGCAAAATAACATAG ACTTAAGTATTTCTTTACAATTTTTGTAATTTCTCAAATTTTAATTTACAATATGATCTTTGGTATTA CATGAATGTTATCTGGGTATGCTATAATTCTATAATTTTTTTTTAAAGTTTCCTTACACTTAGCAGTT GAGAAGCCCTCTAGCAGAGGTTTCTGAGGTTTAGAGGTTTCCTGGGAAACCTAGAATTGCCGCCTAAG ATAGGATAGCTGCCTCTCCCCTACATCTTATACTCTTGCAGTAGGTGTTCAGTAAATATTTGTGGAAT AAATACTTCAGTCGTTGAAAGGAGACGTGGTTTTAAAAAGTGGATTTACAAAGAGACCGTTTTGCAAG AAAAGAAGCTGGTCTGGGGGTCCCCGCAGGAGGCGGGGTTCCGTGCAACAGATACCAAGATGCCTCCA GGGCGGACCACGACCCAGCGGGCCGCCGGAAGGCTCCTTACCTGGCCGCAGCCGGACCCTCCTCAGGG AAGCAACTGCCTCCAGGGACTCCGCGGGGCTGTCGGGCGGTTGCCGGGGAGACCTCTGGCCGCCACGC ACCTGCTGCTTGGTGGGGCGGGGCCTCGAGAGGCGGGGCTGTAGTTCTTTGTCATTTCTTTTCCAATT CGAAATAGTCACTTTTGTACCTAATTTGGCATTTATAATTATAATACACTCATTTTCACAACTATGGA AGAGAGGGTACGCGCATGCCCATTTATGTCGCACACATGAAATGAAGAAACCTCATTTCAAGCGCGGC TCCGCCACACTGCGCTAGTCTCTGTCGACAACTTCAAGTGGCTAGCCTCACGCACAAACGTGTGGCAA AGCCACACTTTCCAGCTTTAGGTGATTTTAAAACAATTTCTTGGGCCACACAGCGTAGGTACAACATG GATTAGAGGTGAGGGGAAAACTGACACTCAGTGAAGGACCGTCAGAGGGCCGGCTTCCAGGAAAATGG GCCGCAGCAGGCAGGGAAAACACAAGGATCTATCCTGCAACTCGGAGAACCCTTTTCAAAAGAAGCTA CCCAATCCCAAACCTTCCGCTTTTTTCCAAAGAGAGGGAGGAGATAAATAGACTCAATTAATCCGTCG ACTTTTTCTCCGCCCATGTTTTCCTCCAATCCTTACCAAAGATGGTGCCCTTCGCTTCCTCTCTCGGC AGCACGCAGGTCCCGGGAGCCTCTACCCGACCTCTCTATGATACGTCCTCCAGCCCCGCTCCCGACGT GAGGGGCGGGGCTTGCCTGGAGGCGGGGCGCAGGGATCCGGAAACACC

ATGCCCACGGCAGCGGCTCCAATAATCTCTTCCGTTCAAAAGCTTGTTTTGTATGA AACTCGCGCGCGGTATTTTCTTGTAGGTTCAAATAATGCGGAAACAAAGTACAGAGTACTGAAGATAG ACAGAACTGAGCCTAAGGACCTTGTCATAATCGATGATAGACATGTTTATACGCAACAGGAAGTGCGG GAACTCTTGGGCAGATTGGATTTGGGGAATAGAACAAAAATGGGGCAGAAAGGTAGCTCTGGGTTGTT CCGAGCTGTCTCAGCTTTCGGCGTAGTAGGCTTTGTGAGATTTCTGGAGGGCTATTACATAGTGCTTA TTACCAAAAGGCGCAAGATGGCGGATATAGGCGGCCATGCGATTTACAAGGTTGAGGATACAAACATG ATATACATACCAAATGATTCAGTGCGAGTCACCCATOOTGATGAAGCTCGCTACCTGCGCATATTTCA GAATGTCGATCTGTCTAGTAACTTCTATTTCTCCTATAGTTATGATCTTAGTCATAGTCTCCAATATA ATCTCACCGTCCTGCGGATGCCCTTGGAGATGCTCAAATCCGAGATGACACAGAACCGACAAGAAAGC TTCGATATTTTTGAAGACGAAGGTTTGATCACACAGGGAGGTAGCGGTGTATTCGGAATTTGTAGTGA ACCCTATATGAAGTACGTATGGAATGGCGAGCTCCTGGACATTATAAAAAGCACGGTCCACAGAGACT GGTTGCTTTACATCATTCATGGCTTCTGCGGCCAGTCTAAGTTGCTGATTTACGGGCGGCCTGTGTAC GTAACTCTGATCGCAAGGCGATCTTCTAAATTTGCGGGCACCAGATTTCTCAAGCGAGGCGCCAACTG CGAGGGAGACGTAGCTAACGAAGTTGAGACTGAACAAATTCTGTGCGACGCGTCCGTTATGAGTTTTA CAGCAGGTTCCTACTCCTCCTATGTACAAGTACGGGGCTCAGTTCCTCTCTACTGGAGTCAAGACATT AGCACTATGATGCCCAAACCCCCAATTACCCTCGACCAGGCCGACCCGTTCGCTCACGTTGCGGCCCT GCATTTTGATCAAATGTTCCAACGATTCGGCAGCCCGATTATCATTCTGAATCTTGTGAAGGAGCGGG AAAAGAGGAAGCACGAGCGGATCTTGTCTGAGGAATTGGTGGCAGCCGTGACATATCTGAACCAATTC CTGCCACCGGAGCACACGATAGTATATATTCCTTGGGACATGGCTAAGTACACAAAATCTAAATTGTG CAATGTGTTGGATCGCCTTAACGTGATCGCGGAAAGCGTAGTCAAGAAGACAGGTTTTTTCGTAAACA GGCCCGATTCATACTGTTCAATTCTCCGACCTGACGAGAAATGGAACGAACTGGGGGGATGCGTGATA CCTACTGGTCGCCTGCAGACTGGTATTCTCAGGACGAATTGTGTAGATTGCCTCGATCGGACGAATAC AGCGCAATTTATGGTAGGGAAGTGCGCGCTGGCCTACCAGCTGTATTCACTGGGGCTGATAGACAAGC CGAATTTGCAGTTCGACACCGATGCGGTGCGCCTCTTTGAGGAGCTCTATGAGGACCATGGAGATACA CTCAGTCTCCAGTATGGAGGGTCACAACTCGTACATCGAGTTAAAACATACAGGAAGATCGCCCCATG GACACAACATAGTAAAGATATTATGCAAACCTTGTCCAGATATTATTCCAACGCCTTCAGCGATGCCG ATAGGCAAGATTCAATCAATCTCTTTCTGGGGGTGTTCCATCCCACTGAAGGTAAGCCCCACTTGTGG GAGTTGCCTACAGATTTTTACCTTCATCATAAGAACACCATGAGACTGCTCCCAACACGGCGGTCTTA TACGTACTGGTGGACACCTGAAGTTATTAAGCACCTCCCCCTCCCGTATGACGAGGTGATCTGCGCGG TTAATCTCAAAAAATTGATTGTGAAGAAATTTCATAAATACGAAGAGGAAATTGATATCCATAACGAA TTTTTTCGCCCATACGAACTGTCCTCTTTTGATGATACATTCTGTCTTGCCATGACTAGTTCTGCGAG GGATTTTATGCCTAAAACGGTCGGAATCGACCCGAGTCCATTTACCGTTAGGAAACCTGACGAGACGG GGAAGTCAGTATTGGGGAATAAGAGCAACCGAGAAGAGGCGGTGTTGCAGCGGAAGACCGCAGCTTCT GCTCCTCCGCCCCCATCCGAGGAGGCTGTGAGTAGCTCTTCAGAAGACGATTCCGGCACCGACAGAGA GGAAGAGGGATCAGTTAGTCAGAGAAGCACACCGGTGAAAATGACTGACGCGGGCGACTCCGCTAAGG TAACTGAAAACGTCGTGCAACCAATGAAAGAGCTCTACGGTATCAACCTCAGCGACGGCCTTTCAGAA GAGGACTTCTCTATCTACAGCAGATTTGTTCAACTCGGTCAAAGCCAACACAAGCAAGACAAAAATTC CCAACAACCCTGCTCAAGATGCTCCGACGGCGTAATTAAACTGACTCCGATTAGCGCGTTTTCACAGG ATAACATTTACGAAGTACAACCTCCACGAGTTGACCGGAAAAGTACGGAGATATTTCAGGCTCACATC CAGGCCTCTCAAGGAATCATGCAACCCCTCGGAAAGGAGGATTCCTCAATGTACAGAGAATATATACG CAATCGATATTTGGATTACAAAGATGACGACGACAAGTA

The CLN5 protein sequence is:

(SEQ ID NO: 32) MAQEVDTAQGAEMRRGAGAARGRASWCWALALLWLAVVPGWSRVSGIPS RRHWPVPYKRFDFRPKPDPYCQAKYTFCPTGSPIPVMEGDDDIEVFRLQ APVWEFKYGDLLGHLKIMHDAIGFRSTLTGKNYTMEWYELFQLGNCTFP HLRPEMDAPFWCNQGAACFFEGIDDVHWKENGTLVQVATISGNMFNQMA WVKQDNETGIYYETWNVKASPEKGAETWFDSYDCSKFVLRTFNKLAEFG AEFKKNIETNYTRIFLYSGEPTYLGNETSVFGPTGNKTLGLAIKRFYYP FKPHLPTKEFLLSLLQIFDAVIVHKQFYLFYNFEYWFLPMKFPFIKITY EEIPLPIRNKTLSGLDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for CLN5 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

CLN5 DNA

(SEQ ID NO: 33) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG CTTGGTTATGTCAGTTCCTGTGTGTAGACA GTAAGAAAAAAAAAGCCATGCTATGTGTGACATTTTTTTCCAATGTTTATTTCCCACCAAAAAGTAAA TGCATTTTAACCCATTCTGTGGTTCACTGTAGCTTAAGGAAACCAAGCATATAGATGCATTAGTGATT TTGTTTATATTATGTAAAATGTAACGATCTATCTTAGAAATACCACAGTTTGTATTTTTCTTTAAGGA GTAAAGATTTGTCTTTAAAAATAACTTGATATTTTCCTGGCTTTCATTTAATACAATGGAAAATAAAG TATTACACGAAAAAAAAATTTTTTCTTAGAGACAGTATCTCATTATGTTACCCAGGCTGAAGTGCAGT GGCTATTCACAGGCACGATTATAGCTCACTATAGCCTCAAAGTCCTGGGTTCAAGCCTCCTGAGTAGC TAGAACTTCAGGTACATGCCACCTTGCCTGGCTTCCTGCTTTCTTATTCACTAAGAAACTTTGTTCTC TAAAATCATAGATTAGAGACAACTTCGTGTTTGAAATTACATCAGTAACAATAAAATATCCCACCTTT GCTTGAAGGACCTCAGTCATTCCACACAGAGAATTGGCCTCAATTTACAACCCAGATGTCAAGCTTCT GATAAGGGGTTTCCAGACACAAAACTCCATCGCTATTTTAACTTCATAGTCTCCAAGGAAATAGGCCC TTCATCCACTTTGCAGTCTAGACCTAGAGCCTGTGTGTTGATGGCAGCAGCAGGCCGTCTGGAGCAGC CACTACCATCATTGACATACAGCCTTGTTTTGCTTTGAGTCTACCAAAATACTGCTTATTTAAATTTC ATCTCAACTCCACACTTCCCCAGAATCCTATCACTCTATCTGGGGAGATGCCATGTGGTCCAGGCAGT CTTAGGCTGAATGGGCAAGGATCCAAGGGAAACCAATTAGATTGAAATTAGTTCTGTCTGTGGGCCCT CAAGATTTAAAAGCCATGGACAAGGGGGAAGCAACCAGTATCGACCAGCGATAATCTATGAGCACCTT CAGCTTGGGGTGTGGGGTCATAGACAAAAAGAATGGGGTTTAATCAGTGTTCCCATCCAAGGCAAAAC CAGACCAGAAGAATGGGAGCTACCAGGAGGCTGAGTTAAGACCAATACTAGGGCCAGGCATGGTGACT ACAGCCTGTAATCCCAGCACTTTTGGAGGCCGAGGCAGGTGGATTACTTGAGGTCAGGAGTTCGAGAC CAGCCTGGCCAACATGGTGAAACCTCGTCTCTACCAAAAAAAAAAAAAAAAATTACAACTGGCACACA CTTGTACCCAGCCACTAGGGAGGCTGAGGCAGGAGAATTGCTTGAACCCGGGAGGCGGAGGTTGCAGT GAGCCGAAATCACATCACTGCACTCCAGGCTGGGTGACAGAAGGAGACTCCGTCTCCAAAAAAATAAA AAATAAAAACCAATACTAGGAAGTGCTTTCTTACCATGAAAGCTCCCTGCACACAGAATGAAGAGACA GATGGCAGAAGCAAGACCAGAGGCCTCCACCACTGAACAAGGTCAACCTGAATTTGTTTTTGTAGCTC TGGGAAGTCCTGAACTGAATGGGAGGTTCTACTGTGGCCCTCTACTAACAGTAGATGGAACCTGGAAC CATCTACTGTTAATTGTCCTTTTAGTAGCCAAGACATGAAGTACCTATCTCCCTTCTTTGTATTTGGT GAAAAGATTTGAACTCGAGCCATCTCTGCTAAAGGCATGACTTTAGTCACCCCACTGCAGTTGCTTCT CTTTGCCTCCAAGAAAGTCCAATCTGATGGGCAGATTGTGCTTGCAGATGACTGGATTAAACTGCAAA TATCTCATGAAGCTGCTGCCTGCATCACCGCTCTCCAGGCAGCCACGGAGGCTCTGGTTGTTGAGGCC ATCTACTGTGGCCCTCATACATCATACTGTGTATGGTTCCAGGATTTGTAAATGCTCTAATCAATGTT TTTTTTTTTTTTTAAAGCTGTTCCTGCTGATTGCTTTTTAAGCTAGGCTCAAGTGTGGGGCCACGGAA TCCTTCAGGTGCCCTTCAAATCAGACATTACATTTCAGCTCTCAGGGCTAGAATGCTTCCCCCTCTTA TCTTGGGCAGGTCTTTGAAGAAGCCAGTTTAGCCTTGGTAATTTTGAATTTGGCCATAGTATACGGAG GAGAGCTAGGTAGCTATCAAAACGCTTAGACAAACGTATGGTAAAATGCAGCCCAGCCTGAACCTCCG CAAAACCCCCAAACCTGGAGCAGCAAGTGGGCAAAGGAGTGTGTGTTTGGGGCAGGGTACTGAGTCCC ATATGTAATCAAGAGACCTGGAGGGCCCAAGGAAGTCAGTGACACCCCCACAAGCTACATATCCTCCA ATGGATTGTGGTGGTCATCTCCGGCTACCGAAGCCACCTTGCTTATTCCCATAGGCTTACAAACATTA TGATGCTTCACACGAGTTGTGGGTGAAGTGAAGGAATTGGAAAGTCCCGGTCTAAGGCCCTGCAAAAC TGCTGTCTGGTAAAAACAAGTGACTATGGCAAGGCCCTGAATGTACTACGTATAGACTTAAGTCAGTA TTTGTGCCTAACAGCAAAGCATGCCACAAGAGGCTCCTCAAAAGCCGGGTAATTGATGCCATTGTTTT CTTGACCTAGTTGAAGAGTCAAAGAAGAGAAGGTGATGCAGAAACTTCTTTCCAGTGAAGTGACAGAT CCAAGCAAGGAACACCTGCCTGTGAGGGGAGCGGTAGGGGAGGGGGTAGATTCGGCAGCACTCGGGTA GTGGCAGGGACCACATATTGTCGGTGTTAACCACTGTTATCACTGGCCCAGGTCGAGTGAGGACGAGT CATTTCCCCACTAAGCACTTGGGGAGTGGCAGGGACCACATATTGTCAGTGTTAACCACTGTTATGAC TGGCCCAGGTCGGGTGACGACGAGCCATTTCCGCACTATTGTCCCTTCTTCCTCACTGCACCCCCAGC CCTGCACCCTCAGCTCCAAATACACATTCTCGTTCACTCAACGTTTGTTGACACCTAGCGTGGGCCCT GTGGGATGGGGTAAAAGTTCGGTGTTGGGAGGAGCCCCGGTGACAGATTTTTGGTTTTGGTGGTGGCT TTTGGGCAAGGACAGGTCAATTCATAAAAGATGACGCCCCAGGTCTGGATCGAATTCTCCTGGGAGCC AGACCAAAGCACCTTCCTGGACTGCAAAGTGTGGAAGCCGCCGCGGGCCGGGCGCGGGGAGGTGTCAT GCGCCGGAACCTGCGCTTGGGGCCAAGCTCTGGAGCTGACGCGCAGGGGCAAGGCGCCCCGCGTCCCG GACTGGCGGCTCCGCGCATGCTCCTCCCACCGGCGTCGCAGGCCTCGAGAGGCTCCGG

ATGGCTCAGGAGGTCGATACAGGAGAAGGGGGAGAGATGGGGAGGG GAGCGGGAGCGGCGCGAGGCAGGGCAAGCTGGTGTTGGGCACTCGCACTGCTCTGGCTGGCGGTTGTC CCGGGATGGTCTAGAGTGAGCGGCATTCCAAGTAGGAGGCATTGGCCAGTGCCCTACAAACGATTTGA TTTCAGACCCAAGCCAGACCCGTACTGCCAAGCAAAGTATACATTCTGCCCCACTGGCAGCCCCATCC CTGTGATGGAGGGGGATGATGATATAGAGGTCTTTCGGCTCCAAGCCCCAGTATGGGAGTTTAAATAT GGAGATCTCTTGGGCCATCTGAAAATTATGCACGATGCGATCGGGTTTAGATCAACATTGACAGGCAA AAATTACACCATGGAGTGGTATGAACTCTTTCAGTTGGGAAACTGCACTTTTCCGCACCTTCGACCTG AAATGGATGCCCCTTTTTGGTGCAATCAGGGCGCGGCTTGTTTCTTTGAGGGTATAGACGATGTACAC TGGAAGGAGAATGGCACACTTGTACAGGTGGCAACAATCTCCGGTAATATGTTCAACCAAATGGCTAA ATGGGTTAAACAGGATAATGAGACTGGGATATATTACGAAACCTGGAATGTAAAGGCTAGCCCAGAAA AGGGTGCAGAGACGTGGTTTGATAGCTACGACTGCAGCAAGTTCGTCCTGCGGACCTTCAACAAATTG GCGGAGTTTGGAGCAGAGTTTAAAAACATAGAGACTAATTACACACGCATTTTTCTTTATAGCGGCGA GCCCACTTACCTCGGTAACGAGACATCAGTCTTCGGGCCCACCGGAAACAAGACCCTTGGTTTGGCGA TTAAAAGATTTTATTATCCATTCAAACCTCATTTGCCAACTAAGGAATTTCTCCTCTCTCTCCTGCAG ATATTCGATGCGGTCATTGTTCACAAGCAATTCTACTTGTTCTACAACTTCGAATATTGGTTCCTTCC AATGAAATTCCCATTCATTAAAATCACATATGAGGAGATTCCCTTGCCCATAAGGAACAAGACTCTCT CAGGGCTCGATTACAAAGATGATGACGACAAATA

The AGA protein sequence is:

(SEQ ID NO: 34) MARKSNLPVLLVPFLLCQALVRCSSPLPLVVNTWPFKNATEAAWRALA SGGSALDAVESGCAMCEREQCDGSVGFGGSPDELGETTLDAMIMDGTT MDVGAVGDLRRIKNAIGVARKVLEHTTHTLLVGESATTFAQSMGFINE DLSTTASQALHSDWLARNCQPNYWRNVIPDPSKYCGPYKPPGILKQDI PIHKETEDDRGHDTIGMVVIHKTGHIAAGTSTNGIKFKIHGRVGDSPI PGAGAYADDTAGAAAATGNGDILMRFLPSYQAVEYMRRGEDPTIACQK VISRIQKHFPEFFGAVICANVTGSYGAACNKLSTFTQFSFMVYNSEKN QPTEEKVDCIDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for AGA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

AGA-DNA

(SEQ ID NO: 35) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG6 TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG TGTCTCTACTTAAAATACAAAAATTAGCCG GGCATGGTAGTAGGCAGTAGCAATCCCAGCTACTCAGGAGGCTGGGGCAAGAGAATCGCTTGAATGCA GGAGGTGGAGGTTGCAGTGAGCTGAGATTACACCAGTGAACTCCAGCCTGGGCGATAGAGCAAGACTC CATCTCAAAAAATAAATACATACATACATACATACATACAAATATCCATGGAAAAGTTGATATATTGA GACCTTCTATCAGCCATTCCCACTATAGTGTAATTTAGCTGTTTCTCTGACAGGAATTTTTATTTAAG AAGAAAGAATTTGGAGAAATAGACATAGTAGGAGGTAACAGATCAGGCTCTTTCCACCAGAAGAAACA CAAATACCTTAAAAAACAGGAAGAGGCTAGAGAGATCAGTGGGGTACTAAGACCAATTTTCCATGTAT TGTATTTTACAATTTTTGCTAAAGGCATGTCCTAATTCCTTAAGGCTGCATAAAAATACTCAGCCCAG GAGCTAAGGAAAATTTACTCAGAGGACAATGTATGTTTTTCTGGCTTTCTTACCCTGTTTCACCCAAG TTTCCAGTTTCACCTGCCATTGGGTTATGATTACTCCAGCACAGATGACTTGTTCCTCTTCCAAACCC CATGAAAGGAACTTAGAAAATTTGTCTTTATTATATCTTTTAATTAACACTTCCCCAACGGGATAATG ATACTTCTGGGCTATCTTATGTTCTTTAAATTATGTATTTAATTTCCTAGCAATCAATAAGAGCCTTG AAGGTTTTGTAAGTCTCACAACTCCTACCTAGTTTATATTTTTACATTTATTTATTTATTTATTTTTG AGACAGAATCTCACTCTGTTGTCCAGGCTGGAGTGAAGTGGTGCGATCTCGGCTCACCACAATCTCCA CCTCCCGGCTTCAAGCAATTCTGCCTCAGCCTCCCAAGTAGTTGGGACTACAGGCATGCACCACCACG CCCGGCTAATTTTTGTATTTTTAGTAGAGACGGGTTTCACTATGTTGGCCAGGCTGGTCTCGAACTCC TGACCTCGTGATCCACCCACCTCAGCATCCCAAAGTGTTGGGATTACAGGCGTGAGCCATCGTGCCCA GCCTAGTTCATATTTTTAAAGTTTGTATAGATTTATAGATGCTTTTAAAAATTATGTGATTATGTGTC TTGCCTTGGCAACCTGGGCAGGCATTCCAGACACCCAAAGGGATTATTAGTTCATGTTCGCACGTCTG CCCAGCAACAAAACTGAGCAGCCTCCACCAAGCACGTAAAATCCCCATTCCTCCTCTTATTCATTTAT TTAGCACTTAATAGTGCCAGGCAGGAAGGTAAAAATACATTTAAAAAGGAATGGAGGTAGCCGTCTTG CCCTGGAGGTGCAGGAAGCTGCACTTCAGTGTGCTAGGTAGAGGGTACATAGGCCGTTTCTGTTTTTC TTCCAGCTCAGGGATTTATAATGAGAGGAAGTGCTACAAAAAGCTGTGGTGCGAAAATGACGGACGCT ATGAATGGAAAAAAAATCTAAAATCAATCCGGTCCTAAGCAAACACGCTTCACCTACACTCATAACTA TTGCAGACCTCCGAGGCCTGGGATCCCCAAGAATATACTGAGTTTGACAAACTTTTCAACTTCAACTT TAAATTAAAAAGACAGTAAAAGAACCAAATCCATAGTACACAGCAATCGGCTAAAGTTCCTGGGGCCC TGCAACCCAGAGTTGAATAATTTTGTATTAAATTCCCAATATCAAGCTAAATCTATTTTAACCACAGG AAAAGCAGCAACTTGTCTGGCTATTTTAAAAATCTGAACAGCACTTAGGAAGAAGCACCTTAGCGCAG GGAACAGCTCAGTGCCCCGTGACACAACTCTCCCGCGGGCCCAGGGACGCCTCGTCTCGCGAGAGTTG AGGGACGCCTGAGCGAACCCCCGAGAGAGCGGGCGTGGGCGCCAGGCGGGCGGGGCACTGGGGAT

ATGGCCCGCAAAAGTAACCTTCCCGTTCTCCTGGTACCG TTCTTGTTGTGTCAAGCACTTGTACGCTGCTCTTCACCGCTCCCGCTTGTCGTTAACACCTGGCCTTT CAAGAATGCAACAGAGGCGGCATGGCGAGCACTCGCATCTGGCGGGTCTGCCCTCGATGCAGTAGAGT CCGGCTGTGCCATGTGCGAAAGGGAACAGTGTGACGGGAGTGTGGGATTTGGCGGCTCTCCAGATGAG TTGGGAGAAACGACCCTTGATGCGATGATTATGGATGGAACAACCATGGATGTGGGGGCGGTCGGTGA CCTCCGCAGGATAAAAAATGCTATTGGGGTGGCGAGGAAAGTCCTGGAACACACCACCCATACTTTGC TCGTTGGTGAGTCTGCAACAACGTTCGCGCAAAGCATGGGCTTTATAAATGAGGACCTGTCCACAACT GCCTCTCAGGCTTTGCACTCTGACTGGTTGGCGAGGAATTGCCAACCCAATTACTGGAGAAATGTTAT TCCCGATCCATCCAAGTATTGCGGGCCTTATAAGCCACCGGGAATCCTTAAACAAGATATACCTATTC ATAAGGAAACCGAGGATGACCGGGGACATGATACGATCGGAATGGTAGTGATCCACAAGACAGGGCAT ATTGCGGCGGGGACCAGCACAAATGGTATCAAATTCAAAATTCACGGTCGAGTCGGTGACTCCCCCAT ACCTGGTGCCGGGGCTTATGCTGACGACACAGCTGGAGCTGCTGCCGCGACAGGTAATGGTGATATCC TGATGCGGTTTCTCCCATCATACCAGGCTGTCGAATATATGAGACGGGGTGAGGACCCCACTATAGCC TGTCAAAAGGTTATTTCTCGGATACAGAAGCATTTTCCGGAGTTTTTCGGTGCAGTTATCTGCGCCAA CGTTACTGGTAGCTATGGAGCTGCATGTAACAAGTTGAGTACGTTTACCCAATTTTCATTCATGGTTT ATAACTCCGAGAAAAATCAGCCGACTGAGGAAAAGGTTGACTGTATTGACTACAAAGACGACGACGAT AAATA

The IDUA protein sequence is:

(SEQ ID NO: 36) MRPLRPRAALLALLASLLAAPPVAPAEAPHLVHVDAARALWPLRRFWRST GFCPPLPHSQADQYVLSWDQQLNLAYVGAVPHRGIKQVRTHWLLELVTTR GSTGRGLSYNFTHLDGYLDLLRENQLLPGFELMGSASGHFTDFEDKQQVF EWKDLVSSLARRYIGRYGLAHVSKWNFETWNEPDHHDFDNVSMTMQGFLN YYDACSEGLRAASPALRLGGPGDSFHTPPRSPLSWGLLRHCHDGTNFFTG EAGVRLDYISLHRKGARSSISILEQEKVVAQQIRQLFPKFADTPIYNDEA DPLVGWSLPQPWRADVTYAAMVVKVIAQHQNLLLANTTSAFPYALLSNDN AFLSYHPHPFAQRTLTARFQVNNTRPPHVQLLRKPVLTAMGLLALLDEEQ LWAEVSQAGTVLDSNHTVGVLASAHRPQGPADAWRAAVLIYASDDTRAHP NRSVAVTLRLRGVPPGPGLVYVTRYLDNGLCSPDGEWRRLGRPVFPTAEQ FRRMRAAEDPVAAAPRPLPAGGRLTLRPALRLPSLLLVHVCARPEKPPGQ VTRLRALPLTQGQLVLVWSDEHVGSKCLWTYEIQFSQDGKAYTPVSRKPS TFNLFVFSPDTGAVSGSYRVRALDYWARPGPFSDPVPYLEVPVPRGPPSP  GNPDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for IDUA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

IDUA-DNA

(SEQ ID NO: 37) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG TCCAGGGAAGGTGTACTTTTCTGTCCACAG GTGTCCCGGTGAGCGGCTCACCTTAATTCTCTCAGGGCTTGAGGTGATTTAAGGCTGGCTTCAGTCCC CACAAAGACAATTCTGTTGCTGGTTTACCTTTGCTTTTAGGGGATAGAACTTTGGGGTCCCAAGAAAA ACCCAAAGTCTTTACCAGGCCCCCCGCCTGAGCCTCGACTTCTGTCCTGTGGCCACAGTGTGAGGAAC GAACGCAGCAGCGTGTCGCCATGTCTTGTGTGGCTGGGATACGCTGCAGGGGTGTGGAGTCGCCGCCC CAAAGCGGGCCCCGCCCCCTCCCGGCTTGTCCCTGCAGAGCCCCGAGGCCTCAGAGGCTCCTCAGAGC TCCCAGTGCCCTGGACGGTTCCGTTCAGCGCTCTCCAGTTCTGATGGTTGCTCTCAGGAGGCGGCTGG TCTGAAACAATTCAGTTTCCATTGCTGTGTCCTGCACCACGGTGTGGGACTGGTGGTTTCTTACTGTT TTTCTCAGTTCTCTGACGCTTTGAGGAATTGTTTTTAAAGCGAGTTATCCATCATTTTAGTTGTTTTC TCTGGGGTCGTTGGACTGAGGGTCTTACCCCGCTGTTCCTGGAGACAGTTCTGTACTTGCATGGTTTC TCTCGCCTTTCCCTCCCTTTCTTACTTTTTAGTTTCTTAATGAATTTTTTTGTATTATGTTTTTCCTC CTTGCTAATTTGGAATATATACACACTATTTCACTTTTAAATGGCTAATCACTTTTAATGCAATTTCA ACATAAGAAGACCTAATGTTAAGCAATATTTTAACCCCTCTCCCCAAAATAAAAAGACCCAGAACACT GTAACTCTAATTATCCTTCTCCCAACTTAGAGAGGATTATTGTCCAGTATTTTCGTTTTGTTAGTAGA CTGTTCTTTTTTTCTTTTCTTTTTTTAGAGATGGGGTCTCATTTTGTCAACCAGGCTGGAATGTAGTG GTGTGATCATGGCCCGTCTCAGCCTTGAACTCCTAAGCTCAAGCAATCTCCCACCTCAATTTCGTGGG TAGCTGGGCCTCACAGGCATATACCATCGCATCTGGCTAAATTTTTTTTTTGTACAGATGGGGTCTTG GTACATCTCCCAGGCCGATTTCAAACTCCAGGCCTCAAGTGATCCTCCCGTGTTGGCCTGCAATTCCA AAGTGCTGGGATTGCAGGTGTGAGCCACCGCACCAAGCCTGTTCTTTCCATTATTATTTTTATACAAT GTTTGCTTGGATTCACACATGCATACATGGACTACACATGTACTACAGTTGTCCCATGGTATCCTCGG GGTATTGGTTCCAGGACCCTCCCAGATACCAAAATTTGCAGGTGCTCAAGTACTTGATATAAAATGGC ACAGTATTTGCACATTACCTACGCACATCCTACTGTGTAGTTTAAATCAAGATTACTTATAGTCCCTA AAACAATGTAAATGCTCTGTAAATAGCTGTTATACTGTATTGTTTTAAAATATGTATTATTTCGTATT GCTTTGGCTTTAAAACAATATTTTCAGTCTGCTTGGTTGAATCCATGGATCTGAAGCCAAGTGTAAGG AGGGCCCAGTGTGCTCTTCTGGGGTAATTCTCCTTCCTGCTAAAGCGCACGCTTTACTCAGGAGGCTG GGGTGAGAAAATCGCTGAAGCCCCGGAGATGGAGGTTGCAGTGAGCTGAGATCGCGCCACTGCACCTC AGCCTGGGCGACAAAGCAAGACTCTGTCTCAAAAACACACAAAAACAGAGAAAAACAAGACAGTAATG GCTCAACTCACATAGCACCAACGGGCGAAGCGTTCTTCTGAGCGCTTTCCGAGTCATCGGTCCTCAGA GCAGCCCCTGAGGCCCGCAAGGAAGCGGGGCTCCAAGCCCTGCCGTGCTCCCGGCTCCCCGAGGCTCC CCGAGGCCACCCAACCCCTCCCACCCGGCCATCGCCCCCTCACCAAGGCCCCGCCCCGCGGCGGCGGT CACATGGGGTGCGCGCCCAGACTCCGACCCGGAGGCGGAACCGG

ATGAGGCCACTGAGGCCAAGAGCTGCACTTCTGGCGCTCTTGGCGAGTCTTCTCGCCGCA CCTCCCGTTGCCCCTGCGGAGGCACCACATCTCGTTCATGTTGACGCTGCGAGGGCTTTGTGGCCACT TAGGCGATTCTGGAGAAGTACGGGCTTCTGTCCACCGCTGCCGCACTCACAGGCAGACCAATATGTCT TGAGCTGGGATCAGCAACTCAACTTGGCGTATGTGGGAGCTGTCCCGCATCGCGGTATTAAGCAAGTG CGAACGCATTGGTTGCTTGAGTTGGTAACCACGAGAGGTTCCACTGGGCGAGGGCTCTCCTATAACTT CACACACCTCGATGGGTATCTGGACCTGCTGCGAGAAAATCAACTCCTTCCCGGGTTCGAACTGATGG GCTCCGCATCTGGCCACTTCACGGACTTCGAAGATAAGCAGCAGGTCTTCGAATGGAAAGATCTGGTG TCAAGTCTGGCTCGCAGGTATATTGGACGATACGGTCTGGCCCACGTCAGTAAGTGGAATTTTGAAAC GTGGAACGAACCAGACCACCATGACTTTGATAACGTATCTATGACTATGCAGGGATTTCTCAATTACT ATGACGCTTGCTCTGAAGGACTCCGGGCTGCAAGTCCAGCTCTCCGCTTGGGCGGGCCTGGGGATAGT TTCCATACACCTCCCCGATCCCCGTTGAGTTGGGGGCTCCTCCGACATTGTCACGACGGGACGAACTT TTTCACCGGTGAAGCGGGAGTTCGGCTCGATTACATCTCTCTGCATCGGAAGGGCGCAAGAAGCTCCA TAAGTATCTTGGAGCAAGAGAAAGTCGTGGCGCAGCAGATCAGACAGCTCTTCCCGAAGTTTGCGGAT ACACCTATATACAATGATGAGGCTGACCCACTGGTCGGCTGGAGCCTGCCCCAGCCGTGGAGGGCTGA CGTAACATACGCCGCGATGGTGGTTAAGGTAATAGCCCAGCACCAGAATCTTCTGTTGGCAAATACCA CGAGTGCATTCCCTTATGCTCTGTTGTCAAATGATAATGCCTTCTTGTCTTACCACCCGCATCCTTTC GCTCAACGCACGCTGACCGCCCGCTTTCAAGTAAATAACACTCGCCCACCCCACGTGCAGCTCCTGAG GAAGCCCGTTCTGACTGCTATGGGGCTCCTCGCGCTGCTGGATGAGGAGCAGTTGTGGGCTGAGGTAT CTCAAGCCGGGACTGTATTGGACTCCAATCACACTGTGGGGGTTCTTGCTAGCGCGCACCGCCCTCAA GGACCTGCCGACGCCTGGCGCGCTGCAGTGTTGATATATGCCAGTGATGATACGCGAGCCCACCCGAA TAGGTCTGTTGCCGTGACGTTGCGCCTCAGAGGCGTTCCCCCTGGTCCAGGACTCGTCTATGTTACTC GATATTTGGATAACGGCCTCTGTTCCCCTGACGGTGAATGGCGGAGATTGGGGAGACCTGTGTTTCCG ACAGCGGAGCAGTTCCGGCGCATGCGAGCGGCAGAAGACCCTGTTGCAGCTGCTCCACGACCGCTCCC TGCAGGCGGCAGGCTTACTTTGAGACCAGCTTTGAGGTTGCCGAGCCTCCTGTTGGTCCATGTATGCG CGCGGCCAGAGAAGCCACCCGGGCAAGTAACCCGGCTTCGCGCCCTCCCGCTCACCCAAGGCCAGCTC GTGCTTGTATGGAGCGACGAGCATGTTGGATCTAAGTGTTTGTGGACTTACGAGATACAATTTAGCCA GGATGGAAAGGCGTATACCCCTGTGAGTCGGAAGCCTTCTACATTCAACCTCTTCGTGTTCAGCCCCG ACACAGGTGCTGTTAGCGGGTCCTATCGGGTGCGGGCGCTGGATTACTGGGCACGGCCCGGGCCGTTT TCCGACCCTGTTCCCTACCTGGAAGTTCCCGTTCCGCGAGGCCCACCTAGCCCTGGGAATCCAGACTA TAAGGACGACGACGATAAATA

The GDNF protein sequence is:

(SEQ ID NO: 38) MKLWDVVAVCLVLLHTASAFPLPAGKRPPEAPAEDRSLGRRRAPFALS SDSNMPEDYPDQFDDVMDFIQATIKRLKRSPDKQMAVLPRRERNRQAA AANPENSRGKGRRGQRGKNRGCVLTAIHLNVTDLGLGYETKEELIFRY CSGSCDAAETTYDKILKNLSRNRRLVSDKVGQACCRPIAFDDDLSFLD DNLVYHILRKHSAKRCGCIDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GDNF and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

GDNF-DNA

(SEQ ID NO: 39) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG AAACCCTCTTAAGACGGAAGGGAAATCTAG TGCCTCTGTGGCTTCCTGCTGGCGGGCACCGCGATTTGGAATGGCGCATTAACCCCGCGCCTCCATGC TCCTCCGGTCGGACCGCCAGCCATTTCGCACGCACCCGGGAGCTGGCACCGGCGGGGGGCTTGAGGGG GGAAGCTCGCGTTCCCCAGGTCCTAGCTGCCAAAGTACCTTTCTGGGCTCATTTTGCATGGCCTGGTG CAGTTTTCCTGTGTCTGCACATCGCGACCCAGAACCTAGCTTTTTCCCGAGTTTGCAAACCAGCCCGC GAGGCAAGAGGCGCTCGGTGCTGCAGGTCACTAGGAGTTTCTAGTCCCTACACCCTCTCGAGCCCAAC AGCTGCATAGCGAACAAACAGACGCTCAGGAGATGTAAAATGCATTAGTCTCTGCAGAGGTGGGAGGT GGCGGCCGAATTAAAGGCTTCCCCGGGTTGCCTGCACCGGGACAGGGAGTGGGGTTCCGGGTAGAGAT GAGGACTGGAACCCTGGAATGGAGGCGGGGGTGCCTGTGAACTAATGGCTAGGAAAGGCACTGAGGTT TTTGCATTAACCTGGGTTTTGCATTTCCCTCCCGCATGGGAAAAAAAAAATCGAGTTTTTCCTAAGAA CCGTTTTATGGAGCCGGTCGAGGGGATAGGATAATCGACTGCACGAATCTCGCAGATTCCGCTTGAGG AGATTCTCTCTAGGTCACTAGTGCCCTGGAGACGAACCCTGGGATTAGGAAGGCACTGGATAACACTG CACCCCAAGATGCCTCGGTTCTTCCCCGTCTCCTCATTGGTTGGAACTCGCCCCCAAATTTACAGCCC CTTTTTCTAACCCACCCCCAGCTGCGTGGCCCTCCTTTGTAGGGGTGTGAGGATTGAGAAGCCAAACA GAGCCCACCTCGGGCTGAAAAGAGCTGAACCCCCTACTCTGCGCCGTACCACGGTCTAGGCCTTCCAG TGCCAGAGCACC

ATGAAGCTCTGGGATGTCGTGGCG GTGTGTCTTGTCCTTCTCCATACTGCGAGTGCGTTTCCACTGCCAGCTGGGAAAAGACCCCCAGAGGC CCCTGCAGAAGACCGATCTCTTGGGAGGAGGAGAGCACCGTTCGCTCTGAGCAGCGACAGTAATATGC CGGAGGATTATCCCGATCAGTTCGACGACGTAATGGATTTTATCCAGGCAACGATAAAGCGGCTGAAA CGGAGTCCGGACAAACAAATGGCAGTGCTCCCGCGCCGGGAACGAAATAGACAGGCCGCCGCGGCAAA TCCGGAAAATAGTAGGGGCAAAGGAAGACGGGGGCAGAGAGGCAAAAACAGGGGCTGTGTATTGACTG CCATTCATTTGAACGTAACGGACCTGGGGCTTGGTTACGAGACTAAAGAAGAACTGATATTTAGATAC TGCAGTGGATCTTGCGATGCCGCTGAAACCACCTATGACAAGATTTTGAAGAATCTTTCTCGAAACAG AAGACTGGTTTCTGATAAGGTTGGTCAGGCGTGTTGCCGACCCATCGCGTTTGACGACGACCTTAGTT TTCTCGACGATAATCTTGTCTATCATATCCTTCGCAAGCACTCCGCTAAGAGGTGCGGATGCATTGAT TACAAAGATGATGATGACAAGTA

The GLB 1 protein sequence is:

(SEQ ID NO: 40) MPGFLVRILPLLLVLLLLGPTRGLRNATQRMFEIDYSRDSFLKDGQPFR YISGSIHYSRVPREYWKDRLLKMKMAGLNAIQTYVPWNFHEPWPGQYQF SEDHDVEYFLRLAHELGLLVILRPGPYICAEWEMGGLPAWLLEKESILL RSSDPDYLAAVDKWLGVLLPKMKPLLYQNGGPVITVQVENEYGSYFACD FDYLRFLQKRFRHHLGDDVVLFTTDGAHKTFLKCGALQGLYTTVDFGTG SNITDAFLSQRKCEPKGPLINSEFYTGWLDHWGQPHSTIKTEAVASSLY DILARGASVNLYMFIGGTNFAYWNGANSPYAAQPTSYDYDAPLSEAGDL TEKYFALRNIIQKFEKVPEGPIPPSTPKFAYGKVTLEKLKTVGAALDIL CPSGPIKSLYPLTFIQVKQHYGFVLYRTTLPQDCSNPAPLSSPLNGVHD RAYVAVDGIPQGVLERNNVITLNITGKAGATLDLLVENMGRVNYGAYIN DFKGLVSNLTLSSNILTDWTIFPLDTEDAVCSHLGGWGHRDSGHHDEAW AHNSSNYTLPAFYMGNFSIPSGIPDLPQDTFIQFPGWTKGQVWINGFNL GRYWPARGPQLTLFVPQHILMTSAPNTITVLELEWAPCSSDDPELCAVT FVDRPVIGSSVTYDHPSKPVEKRLMPPPPQKNKDSWLDHVDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GLB1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

GLB1-DNA

(SEQ ID NO: 41) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG AATCAATACACTAATACAAAACTATTATTT AATATTTAGACCGTGTACCATTATCAAAATCAGAAAGTTAACATTGATGCGGCCGGGCACAGTGGCTC ATGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGTGGGCAAATCACTTGAGGTCAAGAGCTCCAGACC AGCCTGGCTAACATGGTGATACCCCATCTCTACTAAAAATACAAAAATTAGCCAAGCCTAGTGGTGGG TGCCTGTAATCCCAGCTACTTTGGAGGCTGAGGTGGGAGAATCACTTGAACCTGGGAGGCGGAGGTTG CAGTGAGCCGAGATTGTGCCACTGCACTCCAGCCTGGGTGACAGAGTGAGACTCTGTCCCCCCACCCC CCCAAAAAGGAAATTAACATTGATGCATGGTACTAATCTAACCTACAAGTCTAATTCTGATTTCATCA ACTGTCCCACTAACATCCTGTATATACCAAGCTTCTTATCGTCATCATCTCTGGTAATTTCCCCAATT ATCCAGTGAATTTGATATTATTAGCCCTGCTTTACCAACAAAGAAACTAAGCTCAGAGAGGTTAAGTA ATTTGCCCACAGTTACACAGACAGTAAGTGGCAGAGCTGGAATTCCAACTCAAGTGTACTTCCTCCAG AGCCCTTGTTCTTTAATACTGAACTAGAATTGCAGAGCTTGGAAAGGACTTCACAGTGCAAGGACACG GAATTGGTACTACAGGCATGAAAAGAAGCCAGGCACGGTGGCTCATGTCTGTAATTCCAGCATTTTGG GAGTTCCAGGCAGGTAGATTGCTTGATCCCAGAACTTCAAGACCTGCCTGGGAAACGTGGTGAGACCC TGTCTCTACAAAAAATACAAAAATTAGCCGGGTGTGGTGGCGCACGCCTGTAGTCCCAGCCACTTGGT AGGCTGAGACGGGAGAATTGCTTGAGCCCAGGAGGCCAAAGCTGCAGTAAGCCGTGATTGCGCCCCAC TCCAGCCTGGGTGACAGAGTGAGACCCTGTCTCAAAAAACACAAAAACAAAACAAAAAAACAACCCCC CAAACCAAAAAACAAAAACCTAAGAAAAGCCAGTAACTGATACTTTCTCAATCTCTCAATGAAATGTC CTTTCTGATACTTTCTCAATCTCTCAAGGACATGTCCGGTAGGAAAGGAGAAAGGAGTGAACAAATAG AATTTTGGCTACTTTGTTATACAATGTAAAAAGGCTTTTTGGAACACCAAGGCATAAACTAAGGTTAT TTTAAAAAAGAAAATTTTTTTTTGATACGGAATTTCGCTCTTATTGCCCAGGCTGGAGCGCAATGGCT CGATCTCGGTTTACTGCAACCTCCACCTCCCGGGTTCAAGCGATTCTCCTGTCTCAGCCTCCTCAGTA GCTGGGATTACAGGCGCCTGCCACCACGCCCGGCTAATTTTTGTATTTTTAGTAGAGACGGGGTTTCA TCATACTGGTCAGGCTGGTCTGGAACTCCTGACCTCAGGCGATCCGCCCGCCTCGGCCTCCCAAAGTG CTGGGATTACAGGCGTGAGCAGGATTTTCATTCTAACAAGTTCCAGGTGAGTTGATACAGTGGCTCCA GGGACCGACCACATTTTGCTAACCCCCGGCTTAGAGTTATTCAAAGAGCCCGTATATGAGACGCGGAT TCCATCTAGGGCGTTTAGGTTTAATGATTAACAATTTCCCTCTTCTGCTCTCTCAAGGCAGCCAGGGA ACAGGGAGACCATGATTCATGTCCAATCCCCGAGGCGCGTTATCAAGCTGCTGAAAGCAGGCCCTCCG GACTGCAGTTCCAAAGGGTCCCTTCCCAGGGAAGACGCCTGCAAAACCCAGATAGTACTATCCTGGAG TCACGCGGCGGCGCGCAGCCTCCTAGCCGCCCCCACCCGCCCGGCTCGG

ATGCCGGGGTTCCTGGTGAGAATACTTCCCCTGTTGCTTGTGTTGCTCCTGCTTG GTCCCACCAGGGGTTTGAGAAACGCGACACAAAGGATGTTTGAGATTGATTATAGTAGGGACTCATTC CTCAAAGACGGGCAACCATTCCGCTACATCTCAGGCTCCATTCATTACAGCCGAGTACCTCGCTTCTA TTGGAAGGATCGGCTGTTGAAGATGAAAATGGCCGGGCTCAACGCGATCCAAACTTATGTCCCCTGGA ATTTTCATGAACCGTGGCCTGGCCAGTACCAGTTCTCCGAGGACCACGATGTGGAATACTTTTTGAGA CTTGCTCATGAGCTTGGCTTGCTTGTAATTTTGCGGCCGGGGCCTTATATATGTGCAGAGTGGGAGAT GGGCGGACTTCCAGCGTGGCTTCTTGAAAAAGAATCAATTCTGCTCCGGAGCTCAGACCCTGATTATC TTGCCGCTGTTGACAAATGGCTGGGGGTCTTGCTCCCTAAAATGAAACCACTCCTTTACCAGAACGGA GGTCCGGTAATTACCGTTCAGGTTGAAAACGAATACGGTTCCTACTTCGCCTGCGACTTCGACTACCT CCGCTTTTTGCAAAAGCGATTTCGGCACCACCTTGGAGATGACGTCGTCTTGTTTACGACTGACGGGG CTCACAAGACATTTTTGAAGTGTGGCGCCTTGCAAGGTTTGTATACCACCGTTGACTTTGGCACCGGT AGTAATATCACTGATGCATTTCTCTCTCAGAGAAAGTGTGAGCCAAAGGGTCCTTTGATCAATTCAGA GTTCTATACTGGATGGCTGGACCACTGGGGACAGCCTCATAGTACGATCAAGACTGAAGCCGTCGCGT CTAGCCTTTACGATATCCTCGCACGCGGAGCCTCCGTTAATCTGTACATGTTCATCGGTGGGACGAAC TTTGCGTACTGGAACGGAGCAAATTCTCCGTATGCTGCACAACCCACTAGCTATGATTATGATGCTCC TCTGAGTGAGGCGGGCGACCTTACAGAGAAATATTTCGCTCTCAGGAACATCATCCAGAAATTCGAGA AAGTTCCAGAGGGGCCCATCCCACCTTCAACACCAAAGTTCGCCTATGGGAAAGTCACACTGGAAAAA TTGAAAACAGTAGGAGCAGCTCTCGATATACTGTGCCCTTCCGGTCCGATAAAGTCTCTGTACCCACT TACATTCATTCAAGTTAAACAGCATTATGGTTTTGTGTTGTACAGGACTACCCTTCCCCAAGATTGTT CAAATCCTGCACCGTTGAGCTCACCACTTAATGGGGTGCATGATAGAGCGTATGTCGCGGTGGACGGT ATCCCCCAAGGGGTTTTGGAGCGAAATAACGTCATTACGCTCAATATAACTGGTAAGGCTGGGGCCAC CCTGGATTTGCTTGTAGAGAACATGGGGCGGGTTAACTATGGCGCGTACATCAACGATTTCAAGGGTC TGGTGTCAAACCTTACGCTGAGCAGTAACATACTGACTGATTGGACTATCTTTCCTCTTGATACGGAG GACGCTGTTTGTTCTCACCTTGGGGGCTGGGGACATCGCGACTCAGGGCATCATGATGAAGCTTGGGC ACATAACTCCTCTAACTACACGCTCCCCGCCTTTTACATGGGCAACTTCAGTATACCAAGTGGCATCC CCGACCTCCCTCAAGATACCTTTATTCAATTCCCAGGCTGGACAAAGGGTCAGGTCTGGATCAATGGT TTTAATTTGGGAAGATATTGGCCAGCCCGGGGACCCCAGCTGACTTTGTTTGTGCCCCAACATATTCT GATGACGAGCGCTCCCAACACTATAACCGTTCTCGAATTGGAGTGGGCCCCCTGTTCCAGTGACGATC CTGAGCTCTGCGCAGTCACCTTTGTAGACAGGCCAGTCATTGGTTCCTCTGTGACTTATGACCATCCA TCCAAGCCTGTCGAGAAGAGATTGATGCCGCCTCCTCCGCAGAAGAATAAGGATAGCTGGCTCGACCA TGTAGACTACAAAGACGACGACGATAAGTA

The PMP22/MFN2 protein sequence is:

(SEQ ID NO: 42) MLLLLLSIIVLHVAVLVLLFVSTIVSQWIVGNGHATDLWQNCSTSSSGN VHHCFSSSPNEWLQSVQATMILSIIFSILSLFLFFCQLFTLTKGGRFYI TGIFQILAGLCVMSAAAIYTVRHPEWHLNSDYSYGFAYILAWVAFPLAL LSGVIYVILRKREDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for PMP22/MFN2 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

PMP22-DNA

(SEQ ID NO: 43) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG GGAGTTTTCCTCACCTGACTCTGGGAAGGG AAGAGAGTCTGGCCCAGATGGGTAAAGACAAGTGTGTTGGCATCTGGTAGACAGGGCCAGTGGCACAC AACAGTGAACAGCTCTACTGCTGACAGCCAACAGGGACTTCGGGGTTTGGCTGCTGGAGATGGAGGAC CTGGGCAAAAGAGACGTGAGGCCAAGAGAGCAGGTCTCAGAATGTGGAGCTCATGGAAGGAGAGAGGG AGGGCTAATCAGACTGCTCCTATCTGGCCAGAAGCCATGCCCCACACTCACCAGGCCCTACCCCTTTT CCTCTGAATCTTTAGCTCTTAGATCAGAAATAATCTTACGTGTCTTCAGGCTTGATCCTGGCCTGACG GACAGCAGCCTCTGTCGTGTAGCCTTTGGAGCTGATCATGGCAGTACCCAGGAAAAGACTGTCTGGAG AGGCTGCAAAAACCATGCTCACTGTTCCCAGTCCCCGTACAGACCATGTCAGAGGAGGACTGAGGGAG GCTCCTCTCTCTCTCTCTCTGTCACACACACGCACACGCGCACACACACACACACAGATACACGCGCA CACACACACACCGTTTTGCCTGGCAGAACAGACTTATAACTTGCATAATACTGCAGCAGCCCACACTG TACCTCATCTCCATTTGGGTTCCACAACAGAAGGGAGCTGGAAGGAAATCAGCGACAATCTAACTCCA CATGACAACCTGGCTGGACAACGAAACATCCAGCGGGGAGAAAGACACTGGAAATTACCCATACCTGA GCCCCATCCCAAAACACCTGAGTCAGCTTCTCTGACCATGGCCCAGGCTAGGTCATTTGCAAAGCTCT TGAGTGATTCTAAAGAACCACTGCTGTGAAAAATAAAAATGATTTCAGCAAAGAGAGAAAGGTGAAAC TATTTTATTGGCACTGGCTGTGATGCTGGCTGTGAGCAGATGCTGGCTGTGGGCAGAACAGGGGAGAG GGCCATTGAGAGGCCCTTGTGACTGGAGAGTCCAATCAAACGTAAAGTGTGTGACAGGGAGGGACTCC TCCAAATTCTGCAGGTCTCTCCAGACTGGGGATCCCTAACACAAGAGGAAGTCTTATGCCCCAAGTGC CAGAATTCCAGGAAACTCATGCAATGAAACCAGTCCTCTTGTGTCAGAGTTTGCAGCTAGAAGCGGTT CAAGGGATGGAGGACTCTCTGGGAGCTGGAGTGGTACGCTGCAAAGAACCTAAATATGCCATAACTTC CTTTACTTCCCTCTCCAAGAATTTCCAATTGCTCTTCCAGCCTATTCTGCCTGACAGGTTAGAAAGTT TTCAATAGTTTTCAATAGAGGTTCGTTTACTTGCATTGAATTATCTCATGAAGGTCAGCTTGATTCGG GCACATTAAAGACAGAGTCGGAAGAACACATTTCCCTAAGTTTTATTCTAATGTACAACACATGTGAT CATTTGCGATGGGGTCTAGGCAGACAAGGCAGGTAACAGGGAGTCCTTCCAACCAGGGGTTGGAACAA AGGAGGCTTGATTTGGTGACTCTTGAGACATTTGGCTCACTGCTGTGATGCTGTGAGAGATTAGCTGT GCAATGTTTGGGCTCCTTAAAAGGAAGTTTATTTAAAATAAAACTTACCTGCACGTATGTAACACTGT AGACACAGATCCTTCCCACAGTATATTTAATCTCTGCAGAATTCACTGGGAGGGGAGGGGAGCCAGTG GGACCTCTTGGCTATTACACAGGTTGGCACTTCCAGAGAGAACAGTCTTGGCATCACAGGCTTCAGGC ATACTCAAAGCTCTTCTCCCTTCTGATTCCAGTTTCTCCATGCCCTGCAGGGCCTCTTGGGATTATTG TATTCTGGAAAGCAAACAAAGTTGGACACTGTCTCTTTAAATAATAGAGGCTGAGAACCTCTCAGGCC ACCATGACATATCCCAGCATTGGACCAGCCCCTGAATAAACTGGAAAGACGCCTGGTCTGGCTT

ATGCTTTTGCTGCTTCTCTCCATAATAGTGTTGCACGTAGC AGTCTTGGTCCTGCTCTTTGTTTCTACCATTGTATCACAGTGGATTGTGGGTAACGGCCACGCTACCG ATCTGTGGCAAAATTGTAGCACGTCCAGCTCTGGTAATGTACACCATTGTTTCAGCAGTTCACCTAAC GAGTGGCTCCAGTCAGTCCAAGCCACAATGATCCTGAGCATAATTTTTAGCATCCTCAGCCTTTTCCT GTTCTTCTGCCAGCTCTTTACATTGACAAAGGGTGGACGGTTCTACATTACAGGGATATTCCAAATTC TTGCGGGTCTGTGCGTGATGTCCGCCGCCGCCATCTACACCGTTAGGCACCCTGAATGGCATCTTAAC TCCGACTATAGTTATGGTTTCGCCTATATCCTCGCATGGGTGGCTTTCCCTCTTGCCCTGCTTAGCGG CGTAATCTATGTGATTCTCAGGAAGAGAGAAGATTATAAGGATGACGATGACAAATA

The MECP2 protein sequence is:

(SEQ ID NO: 44) MAAAAAAAPSGGGGGGEEERLEEKSEDQDLQGLKDKPLKFKKVKKDKKE EKEGKHEPVQPSAHHSAEPAEAGKAETSEGSGSAPAVPEASASPKQRRS IIRDRGPMYDDPTLPEGWTRKLKQRKSGRSAGKYDVYLINPQGKAFRSK VELIAYFEKVGDTSLDPNDFDFTVTGRGSPSRREQKPPKKPKSPKAPGT GRGRGRPKGSGTTRPKAATSEGVQVKRVLEKSPGKLLVKMPFQTSPGGK AEGGGATTSTQVMVIKRPGRKRKAEADPQAIPKKRGRKPGSVVAAAAAE AKKKAVKESSIRSVQETVLPIKKRKTRETVSIEVKEVVKPLLVSTLGEK SGKGLKTCKSPGRKSKESSPKGRSSSASSPPKKEHHHHHHHSESPKAPV PLLPPLPPPPPEPESSEDPTSPPEPQDLSSSVCKEEKMPRGGSLESDGC PKEPAKTQPAVATAATAAEKYKHRGEGERKDIVSSSMPRPNREEPVDSR TPVTERVSDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for MECP2 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

MECP2-DNA

(SEQ ID NO: 45) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG TCCTTGTTTCTTCCCTTGCTCTATGCCCTA CATCCAATCCTTTTGTTCAGTTCTGAAAACATATCTTGAATCTCACAACTTCTCAGAGCTGCACTGCT GCCACCCTAGTTAAAGCTACCATCAACTCTTTCTCCTAGACTGTTCCAGGGCCTTGCAACTAGCCTTG TGCTGTAGTTTTGTTTCATCACGTCCAGTTCTCCACTCTACACCTGCAACATAGATCAGACAGCTCCT GGCTCAAAATCCTCTGAGGGCTTCTCATCTTAGAATAAACTCTCGGTTCTGGCCGGGTGCGGTGGCTT ACGCCTGTAGTCCCAGCACTTTGGGAGTCCGAGGCGGGCGGATCACTTGAACTCAGGAGTTTGAGACC AGCCTGGGCAACATGGTGAACTCCCATCTCTATCAAAAATACAAAAACTTAGCCAGGCGTGGTGGTTC GCATCTGTGGTCCCAGCTACTTAGGACGCTGAGGAGGGAGGATCGCTTGAGCTCAGGGTGGACGTTGC AGTGAGCCAAGATTGCGCCACTGCACTGCAGCCTGGGTGACAGAATGAGACCCCATCCCCACCCCCCC CAAAAAAGAATGAACTCCCAGTTCTCATAGTGGCCCCAGCTGCCTTTCCAATCACATTCCCTACCACT CTCCAGCAACACTGACTTCCTCGTTAGTCCCCAACATGCCAGGCATAGTCTCTCCTCATGTCCTTTGA ACTTGCCTGGAATGTTCTTTCCCCAGATATTCATATGAGGGAGTAAAATGAGGGTGAAAACCAGCAGA TATCTAAATAGCACCCCCTTCACTTAGTTTATCTTTCTCAAAGCCCTTATCACTATGTGAAATGATAT ATTATACTTATTTGTATGCTAGTATGAATCTTCCCGGCAAGAATGTTAGTTTGCTGTCTGTTCAGTAC CGTGCATCCAGAGCCTGGAAGAGTGCCTGGCACATAGCAGGTAGTCAATAAATGAATGGGGGCAAGCA GCCAAATCAGAATCAGGTTTTCTTGCTAAGCATAGAACTAACAGAAGGATCATTGAATGGATTGGATA ATGACTGGCATCAGGGTAAGGTCCCCTTAACAAACACTCCTGTCCTGAACACCTGGTTAGCTAACAGT TTTCTCATACTCTTATTTTCCCAAAACACAATTGCTGGATCTCAGCTCCAAATCAACTCTTCTAGGAA AGTGAAAAATTGCTGGATCTCAGCTCCCAAATCATATCTTCCAGGCAGAGCTAACATTGCCCCTTATT CACACCTCCACCAAACCATCTGATCCAACAGTGACAGGTGTCACGAGGCCTTGGCATGCACTCTCTTC CCCCGCCAGAGTTCTGCGAAAGCCAGGGTTGCGATTTGTTGTCAGTTTATTCCCCGCCTCTATGAGAG TGTGAGCACTGGGCAGGCTCGGATGAAATAATGCATTGAGTAGGCCTCTGAAACCAAGGCCCCTCAGC TGGGGCAACGTCAGGCTCCAGGGTGGGCAACTTTGCTGCTTCTGCCGAAGATAGTGATATTGAGAAAA TGTGGGTGCAATGAAACGCTTATTGCAGCGCACTCGGTGCATCTGTGGACAGAGGGTCAATCGCCCCT CAGAGCAGCGCAAACAGGCGTCCCAAGCCTAGGCCTTCACTTGCCCCAGCATCCGCAAGGGTCCATTA ATCCTTAACATTCAAATTCCGCCCACTAAACCAGTCCCTCCGCGCCCAAGCCGCCTCTTTTCCCCAAA CGACGGCCGAAAGCAGCCAATCAACAGCTGGAGGGGTCCGCCCCCTTTTCCCTGGCCGAAATGGACAG GAAATCTCGCCAATTGACGGCATCGCCGCTGAGACTCCCCCCTCCCCCGTCCTCCCCGTCCCAGCCCG GCCATCACAGCCAATGACGGGCGGGCTCGCAGCGGCGCCGAGGGCGGGGCGCGGGCGCGCAGGTGCAG CAGCGCGCGGGCCGGCCAAGAGGGCGGGGCGCGACGTCGGCCGTGCGGGGTCCCGGCGTCGGCGG

ATGGCCGCCGCTGCTGCCGCGGCTCCCAGCGGCGGCGGT GGAGGTGGTGAAGAAGAAAGACTTGAGGAGAAATCAGAGGACCAGGATCTCCAAGGTCTCAAGGATAA GCCGTTGAAGTTCAAGAAGGTGAAGAAGGACAAGAAGGAAGAGAAAGAGGGCAAACACGAACCGGTCC AACCTAGCGCTCATCATTCCGCCGAACCAGCAGAAGCGGGCAAAGCAGAAACGAGTGAAGGATCAGGT AGCGCTCCTGCAGTTCCGGAAGCGAGCGCTTCACCGAAACAGCGCCGGTCTATCATCCGGGATCGGGG ACCTATGTACGACGATCCAACGCTTCCGGAGGGATGGACGAGAAAGTTGAAGCAACGCAAGTCCGGAA GAAGTGCTGGCAAGTACGATGTGTACCTGATTAACCCCCAAGGAAAGGCTTTCAGGTCTAAAGTAGAG CTCATAGCTTATTTTGAAAAAGTGGGCGACACCTCTCTCGACCCTAACGATTTCGATTTCACCGTCAC TGGCAGAGGCAGTCCTTCTAGACGCGAACAGAAACCCCCTAAAAAACCCAAGAGCCCCAAAGCCCCCG GAACGGGACGAGGTCGCGGCCGCCCAAAGGGTAGCGGAACAACAAGACCAAAAGCGGCTACATCCGAA GGTGTGCAAGTTAAGCGCGTGCTGGAAAAAAGCCCAGGAAAGCTCTTGGTCAAAATGCCATTCCAGAC CTCACCTGGTGGCAAGGCAGAAGGTGGGGGCGCGACAACGTCCACCCAGGTAATGGTGATCAAAAGAC CAGGCCGCAAGCGAAAGGCAGAGGCAGATCCGCAAGCGATCCCCAAAAAACGGGGCCGAAAGCCAGGA AGTGTTGTCGCTGCTGCCGCGGCCGAAGCAAAGAAAAAAGCTGTCAAAGAGAGCTCCATTAGGTCAGT ACAGGAAACCGTGCTGCCAATCAAAAAAAGAAAAACTCGGGAAACCGTCTCCATAGAAGTAAAGGAGG TTGTCAAGCCCCTTCTTGTTTCCACCCTGGGAGAAAAATCAGGAAAAGGTCTCAAAACGTGTAAAAGC CCGGGTCGAAAGTCAAAAGAATCATCACCAAAAGGCCGGAGTAGTTCAGCCAGTTCTCCGCCAAAGAA AGAACACCACCACCATCACCACCACTCAGAATCCCCTAAGGCCCCAGTGCCTTTGCTCCCACCCCTTC CTCCGCCGCCGCCAGAACCGGAGAGTTCTGAAGACCCCACTTCACCTCCGGAGCCACAGGACCTGTCC TCTTCAGTTTGCAAAGAGGAGAAGATGCCTCGAGGCGGATCTCTGGAATCTGACGGGTGCCCGAAAGA ACCCGCCAAGACGCAACCGGCGGTAGCAACCGCAGCAACCGCGGCCGAGAAATATAAGCATCGAGGAG AAGGAGAACGCAAAGACATCGTTAGCTCTTCTATGCCACGGCCAAACCGGGAGGAACCAGTGGATTCA CGAACGCCGGTCACAGAACGGGTCAGCGATTATAAGGACGATGACGACAAATA

The LAMP2 protein sequence is:

(SEQ ID NO: 46)  MVCFRLFPVPGSGLVLVCLVLGAVRSYALELNLTDSENATCLYAKWQMNF TVRYETTNKTYKTVTISDHGTVTYNGSICGDDQNGPKIAVQFGPGFSWIA NFTKAASTYSIDSVSFSYNTGDNTTFPDAEDKGILTVDELLAIRIPLNDL FRCNSLSTLEKNDVVQHYWDVLVQAFVQNGTVSTNEFLCDKDKTSTVAPT IHTTVPSPTTTPTPKEKPEAGTYSVNNGNDTCLLATMGLQLNITODKVAS VININPNTTHSTGSCRSHTALLRLNSSTIKYLDFVFAVKNENRFYLKEVN ISMYLVNGSVFSIANNNLSYWDAPLGSSYMCNKEQTVSVSGAFQINTFDL RVQPFNVTQGKYSTAEECSADSDLNFLIPVAVGVALGFLIIVVFISYMIG RRKSRTGYQSVDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for LAMP2 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

LAMP2-DNA

(SEQ ID NO: 47) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG GTTTGTTAAAGAAGTGATTAATAAGACTGC CACAGACCTACTGTTTCAGAATCTCTGGGGAATGAGGTACAGGAATCTGTATGTTAAAAAAAAAAAAC CCAAAACCAGATGGTTCTTTTGGAAACTAACACTTGAGAATCAGTGCTTTATTCCAACTCAAGATTTT TAAATGCTTTCATCTGTTGAATATTTTAGGTTTTGTCTGTTCATCTATCAAGTATAGCAAACAGTATG CTTAGTATGAACTCATTACAGAATATTTGTGTGTATGTACATAGGAAAAATATCTGGAAGTATAGATG TGGGTGTGTGTATATATGTGTGTAAATATATATAATAATGTTAATAGTAGGAATACAGATGATCTCTA TTTTTCCGCTTTATCCTTCTGTTTTATTTCTCTCATTTTTTTCTTCCTGTGTTTAAAAAAGATGCTTC TTGTTTCTGAGCTCAATTCCCCCACCTGAGAACAGGGTGCTGTAACTAGGTGAATTTCAAGATCATGT CTTGTTCCGATGGTCCGTGACTCCATACTACCCCCTAGGTTCCCTCGTCCATCTCACAGCATGAACTG CATAGGTAACAACAGTGTTTGGAGAATAAGCATGTATTATTTTTGTATGTATTACGTTTGAGATGCCT AGCAACCGTTTTTGTGCCCGCAAAATTTTTCTCTTCTTTGTCAAGGAGCCAAAACGGAAATAGTCTAC TATCTACGGCCCTCAAAAGTTCCTCCTCTCTCCTTAGCCTTAGAAAATACCGTCCGCCATAGGCATGG GCAAAGACCTCATGGCTAAAACACCAAAAGCAATCGCAACAAAAGTCAAAATTGACAAATGGGATCTA ATTAAAAGAACTTCTGCACAGCAAAAGAAATTAGCATTAGCGTGAACAGGCAACCTGCAGAATGGGAG AAAATTTTTGCAATCTACCCATCTGACAAAGGTCTAATATCCAGAATCTACAAGGACCTTAAACAAAT TTACAAGAAAAAAACAACCCCATCAAAAAGTGGGCAAAGGATATGACCAGACACTTCTCAAAAAAAGA CATTTATGCAGCAACAAACATGAAAAAAAGCTCATTATCACTGATCATTAGAGAAAGGCAAATCAAAA CCACAATGAGATACCATCTCACGCCAGTCAGAATGGTGATTATTAAAAAATCAGGAAACAATAGATGC TGGCGAGGCTGAGGAAAAATAGGAATGCTTTTACACTGTTGGTGGGAGTGTAAATTAGTTCAACTATT GTGGCAGACAGTGTGGCGATTCCTCAAAAATCTAGAACCAGAAATACCATTTGACGCATGCACACGTA TGTTTATTGCAGCACTATTTACAATAGCAAAGACTTGGAACCAACCCAAATGCCCATCAATGATAGAC TAGATAAAGAAAACGTGGCACATATATGCCATGGAATACTATGCAGCCATAAAAAAATGAGATCATGT CCTTTGCAGGGACATGGATGAAGCTGGAAGCCATCATCCTTAGCAAACTAACACAGGAACAGAAAACA AAACACTGCATGTTCTCACTCATAAGTGGGAGTTGAACAATGAGAACACATGGACACAGGGAGGGGAA CAACACACACGGGGGCCTGTCAAGGGGTGGGGGCCAAGGGGAGGGAGAGCATTAGGAGAAATACCTAA TGCATGTGGGGCTTAAAACCTAGATGACGGGTTGATAGGTGCAGTAAACCACCATGGCACATGTATAC CTATGTAACAAAGCTGCACATTCTGCACATGTATCCCAGAACTTAAAGTAAAATTAAAAAAAAAAAAA AAAAAGAAAGAAAAAGAAAAAGAAAATGCCGTCCGCGCATATCTCTCAGGAGCATAGGAAGGGCTGTG AACCAAAAAGCCAGGGCGTGGTCGCCCCGCCCACCGGCCGCTACATCACCACCCCTCTCGCCGCTTTC AAGCGCGGAGATTGGCTGTAAGCAAGAAAGAGCCCCGCCCC

ATGGTCTGCTTTAGACTGTTTCCAGTACCAGGTTCTGGACTCGTGCTGGTGTGTCTTGTACTG GGTGCAGTCCGATCTTACGCCTTGGAACTTAACCTCACTGATTCTGAGAATGCCACTTGTCTTTACGC AAAGTGGCAGATGAACTTTACGGTGCGGTACGAGACCACGAATAAAACTTATAAGACCGTAACGATAA GCGATCATGGGACCGTCACTTACAACGGCTCCATCTGCGGGGACGATCAAAATGGCCCAAAAATCGCT GTCCAATTCGGCCCAGGGTTCAGTTGGATAGCCAACTTCACTAAAGCTGCATCAACCTATAGCATAGA TTCTGTATCCTTCTCTTACAATACCGGAGATAACACAACGTTTCCCGATGCAGAAGACAAAGGCATAC TCACCGTGGACGAGTTGCTTGCTATTAGGATACCGCTTAACGACTTGTTTCGCTGCAATAGTTTGAGC ACCCTTGAAAAGAATGATGTGGTTCAGCATTATTGGGACGTACTCGTTCAAGCTTTTGTCCAGAATGG TACGGTTTCAACCAATGAATTTCTCTGCGATAAGGACAAAACTTCCACAGTTGCCCCAACTATTCACA CGACCGTTCCAAGCCCCACAACGACCCCGACTCCGAAAGAAAAACCAGAGGCCGGAACCTACTCAGTG AATAATGGTAATGACACATGCCTCCTTGCTACGATGGGGCTCCAGTTGAACATCACACAAGACAAAGT TGCGTCTGTCATAAATATTAACCCCAATACCACCCATAGTACCGGGTCCTGTCGATCTCATACTGCGC TTCTCAGACTTAATAGCAGCACCATCAAGTACCTGGATTTCGTTTTCGCTGTAAAAAACGAGAATCGG TTTTATCTCAAAGAAGTAAATATTAGTATGTACTTGGTAAATGGTAGTGTGTTCTCTATAGCGAACAA TAACCTCTCATACTGGGATGCGCCTCTTGGTAGTTCCTACATGTGCAACAAGGAGCAAACAGTGAGTG TCAGTGGGGCATTTCAAATCAATACGTTTGATCTTAGAGTCCAGCCATTCAATGTGACTCAGGGGAAG TACTCTACGGCGGAAGAGTGTTCCGCGGACTCCGATCTTAATTTTTTGATCCCTGTCGCCGTGGGGGT CGCCCTGGGATTTCTGATAATTGTCGTTTTTATAAGCTACATGATAGGCAGGAGGAAGAGTCGGACGG GATACCAGTCTGTGGATTACAAAGATGATGATGACAAATA

The NAGLU protein sequence is:

(SEQ ID NO: 48) MEAVAVAAAVGVLLLAGAGGAAGDEAREAAAVRALVARLLGPGPAADFS VSVERALAAKPGLDTYSLGGGGAARVRVRGSTGVAAAAGLHRYLRDFCG CHVAWSGSQLRLPRPLPAVPGELTEATPNRYRYYONVCTQSYSFVWWDW ARWEREIDWMALNGINLALAWSGQEAIWQRVYLALGLTQAEINEFFTGP AFLAWGRMGNLHTWDGPLPPSWHIKQLYLQHRVLDQMRSFGMTPVLPAF AGHVPEAVTRVFPQVNVTKMGSWGHFNCSYSCSFLLAPEDPIFPIIGSL FLRELIKEFGTDHIYGADTFNEMQPPSSEPSYLAAATTAVYEAMTAVDT EAVWLLQGWLFQHQPQFWGPAQIRAVLGAVPRGRLLVLDLFAESQPVYT RTASFQGQPFIWCMLHNFGGNHGLFGALEAVNGGPEAARLFPNSTMVGT GMAPEGISQNEVVYSLMAELGWRKDPVPDLAAWVTSFAARRYGVSHPDA GAAWRLLLRSVYNCSGEACRGHNRSPLVRRPSLQMNTSIWYNRSDVFEA WRLLLTSAPSLATSPAFRYDLLDLTRQAVQELVSLYYEEARSAYLSKEL ASLLRAGGVLAYELLPALDEVLASDSRFLLGSWLEQARAAAVSEAEADF YEQNSRYQLTLWGPEGNILDYANKQLAGLVANYYTPRWRLFLEALVDSV AQGIPFQQHQFDKNVFQLEQAFVLSKQRYPSQPRGDTVDLAKKIFLKYY PRWVAGSWDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for NAGLU and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

NAGLU -DNA

(SEQ ID NO: 49) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG GGACAACATGGTGAAATCCCATCCCTACAA AGGTTAACTGGGCTTGGTGGCACGTGCCTGTAATCCCAGCTACTCAGGAGACTGAGACAGGAGAATGG CTTGAACCTGGGTGGCTGAGGTTCCCGTGAGCTGAGATTAAAAAAAAAAATCATACTTCCCTAGTATC TAAAGTTGATATCTGATTCCAGGCCTCTTTCAACTTTTTTTGTTTGTTTGTTTGTTTTTTTGATATGG AGTCTCGCTCTGTCATCCAGGCTGGAATGCAAATGGCACGATCTTGGCTCACTGCAACTTCCACCTCC AGCGTTCAAGCGATTCTCCTGCCTCAGCTTCCCAAGTAGCTGGGACTACAGGCGTGTGCCACCAAGCC TGGCTAACTTTTTTTCTTTTTTTTTTTTTTGAGAGGGAGTCTTGCTCTGTCCCCCAGGCTGGAGTGCA GTGGTGTGATCTTGGCTCACTGCAACCTCCGCCTCTCCGGTTCACGCCATTCTCCTGCCTTAGCCTCC CGAGTAGCTGGGAGTACAGGCGCTCGCCAACACGCCCGGCTAATTTTTTGTATTTTTAGTAGAGATGG AGTTTCACCGTGTTAGCCAGGAGGGTCTTGATCTCCTGACCTCGTATCCGCCCGTCTTGGCCTCCCAA AGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCAGCACCTGGCTAACTTTTGTATTTTTAGTACAGA CGGGGTTTCACTGTATGTTGGCCAGGCTGGTCTCAAACCCCTGACTTGAGGTGATCTGCAAGCCTCAG CCTCCCAGAGTGCTGGGATTACAGGCGTAAGCCACCGCTCCTGGCCTAAGGTTGGCTATTTTTATGGT TATTTCTTGATTATATGATAAACAAGGGGTGGGTTAGTAATGAATTTTTCAGAAAAGGGGTGGGGATC CCCCCCAACTGAAGGTTCCTCCACTGTTTAGACCATATAGGGTAACTTCTGGACGTTGCCATGGCATT TGTAAACTGCCTGGCGCTGCTAGGAGTGTCTTTAGCATACTAATGCATTATAATTAGCGTATAATGAG CAGTGAGGACGATCAGAGGTCACCTTCCTGTCTTGGTTTTGGCAGGTTTTGACCAGTTTCTTTGCTGC ATTCTGTTTTATCAGCGGGGTCTTGTGACCTTTTATCTTGTGCTGACCTCCTGTCTCATCCTGTGACG AAGGCCTAACCTCCTGGGAATTCAGCCCAGCAGGTCTCTGCCTCATTTTACCCAGCCCCTGTTCAAGA TGGAGTCGCTCTGGTTGGAAACTTCTGACAAAATGACAGCTCCTGTTATGTTGCTGCTGCTGCCGCCA ATGGACAGCCTTTAACGTGCCCGCCAGCCCTGCTCCACCGCCGGCCTGGGCTCACATGGCCCCATCCC TCCTCGAACCTCCTAGCCTGTTAGTTACTCAAATCTGCAAGCTCTCTGCCTTCTCAGGGCCTTCAATA AATGCATTTCTTCTGTCTGGAAGGCTCTTCCTTTCCCTCTTCTAGCCAATTCCTATTCATCCCTGAGT TTCAGATTAAAAGTCACTTCCTTTGGAAACCTTACTTCGCTACTTCGCTACTTACTGCACTACTTCGC AGCATCACAACTATGATGGAAATCCTTACTTACGTTAAATATCTGGTTTCTAGGTCACCTCCCTGACG GGGACGGTAGGGACCGTCTTCTCGTTCATCAGTAGGGAAGTAGCTATGGCAGTGCCTGATACAAAATA AACTCCAAATGTGTATTTATTAGATGGTTGGATGGAAGTTATTTGCGTGTGAAAGCGCGTTTTACCCG AAGGCGCTCTGTGAGGGCCAGCGGGTCCCCTTCGGCCCTGGAGCCGGGGTCACACGCTCCCCACCGCG TGCGGTCACGAGACGCCCCCAAGGGAGTATCCTGGTACCCGGAAGCCGCGACTCCTGGCCCTGAGCCC GGGCTTAGCCTTCGGGTCCACGTGGCCGGAGGCCGGCAGCTGATTGGACGCGGGCCGCCCCACC

ATGGAGGCGGTAGCCGTTGCCGCTGCCGTCGGAGTACTT TTGCTCGCAGGAGCAGGTGGTGCAGCTGGTGACGAGGCTCGGGAGGCAGCGGCCGTACGCGCACTGGT AGCTCGGCTGCTGGGGCCAGGTCCCGCAGCTGACTTTAGCGTGAGTGTGGAGCGGGCCCTCGCTGCGA AGCCAGGCCTTGATACCTACTCTCTGGGCGGGGGAGGAGCGGCACGCGTGAGAGTTCGGGGAAGTACC GGGGTGGCTGCGGCGGCGGGCTTGCATCGGTATCTTAGGGACTTTTGTGGGTGTCACGTCGCCTGGTC AGGTAGCCAACTCAGGCTGCCACGACCTTTGCCAGCAGTACCCGGCGAGTTGACGGAAGCGACGCCAA ATAGGTATAGGTACTATCAAAACGTCTGTACCCAGTCTTATTCTTTTGTATGGTGGGATTGGGCTCGC TGGGAACGAGAAATAGACTGGATGGCACTTAACGGCATCAATCTTGCGTTGGCCTGGAGCGGGCAGGA GGCAATCTGGCAGCGAGTGTATCTCGCATTGGGGCTCACACAGGCTGAAATAAATGAGTTTTTTACCG GTCCCGCCTTCTTGGCTTGGGGCAGGATGGGTAATCTCCATACGTGGGATGGACCGCTCCCACCTTCA TGGCATATAAAGCAGCTGTACCTGCAACATAGGGTGTTGGACCAAATGAGGAGCTTTGGAATGACACC GGTACTTCCGGCATTCGCCGGTCACGTTCCTGAAGCGGTCACGCGAGTATTTCCGCAAGTGAATGTAA CAAAGATGGGTTCATGGGGACACTTCAATTGTTCATATTCATGCTCTTTCCTGCTTGCGCCGGAAGAT CCTATTTTTCCTATCATTGGAAGTCTGTTCCTTCGGGAATTGATCAAGGAGTTTGGAACAGATCACAT ATATGGAGCAGACACTTTTAACGAAATGCAACCTCCGTCTAGCGAGCCCTCTTATCTGGCAGCTGCGA CCACGGCGGTGTATGAAGCGATGACAGCTGTCGATACGGAAGCAGTCTGGCTCCTTCAAGGTTGGCTG TTTCAACACCAACCGCAATTTTGGGGACCAGCCCAGATTAGGGCTGTGTTGGGTGCTGTGCCCCGGGG TAGGCTCTTGGTGTTGGATCTTTTTGCGGAGAGTCAGCCTGTGTATACCCGAACGGCGAGCTTTCAAG GTCAGCCGTTTATCTGGTGTATGCTTCATAACTTTGGCGGGAACCATGGTCTTTTCGGTGCCCTTGAA GCCGTAAATGGGGGGCCAGAGGCTGCTCGATTGTTTCCTAACAGCACTATGGTAGGAACAGGTATGGC ACCCGAGGGTATTAGTCAAAATGAGGTCGTATACAGTTTGATGGCAGAACTTGGGTGGCGCAAAGATC CCGTACCTGATCTGGCAGCGTGGGTTACGAGCTTCGCGGCTCGAAGGTACGGAGTAAGTCACCCAGAC GCTGGGGCCGCCTGGCGGTTGCTCCTGCGATCCGTCTACAACTGCTCAGGTGAGGCATGCCGCGGGCA CAATAGAAGCCCACTCGTCCGACGACCATCCCTTCAAATGAACACTAGTATCTGGTACAACAGGTCTG ACGTATTCGAGGCATGGCGCCTCCTCCTCACTAGCGCACCGAGTCTGGCTACCTCCCCCGCGTTTAGG TACGACCTTCTGGACTTGACCAGACAAGCTGTGCAGGAGCTCGTGTCACTTTACTACGAAGAGGCCAG ATCTGCATATCTGTCTAAGGAACTGGCATCCTTGCTTAGAGCGGGTGGGGTTCTGGCTTACGAACTCC TTCCAGCACTGGACGAGGTGCTCGCGAGTGACAGTAGGTTTCTCCTCGGGTCATGGCTGGAACAAGCA AGGGCCGCGGCCGTTTCTGAAGCCGAGGCTGACTTTTACGAACAGAACTCTCGATACCAGTTGACGCT GTGGGGACCCGAGGGGAATATCTTGGATTACGCGAACAAGCAGCTGGCAGGTCTGGTAGCCAACTACT ATACGCCGAGGTGGAGGCTCTTCCTCGAGGCTCTTGTCGATTCCGTCGCCCAAGGGATACCCTTTCAG CAGCACCAATTCGACAAGAACGTTTTTCAACTGGAACAGGCTTTCGTACTTTCCAAACAACGCTATCC CAGCCAGCCTCGGGGTGACACAGTTGACCTGGCAAAAAAAATCTTCCTTAAATACTATCCAAGATGGG TCGCCGGTAGTTGGGATTATAAAGATGATGATGACAAGTA

The ARSB protein sequence is:

(SEQ ID NO: 50) MGPRGAASLPRGPGPRRLLLPVVLPLLLLLLLAPPGSGAGASRPPHLVFLL ADDLGWNDVGFHGSRIRTPHLDALAAGGVLLDNYYTQPLCTPSRSQLLTGR YQIRTGLQHQIIWPCQPSCVPLDEKLLPQLLKEAGYTTHMVGKWHLGMYRK ECLPTRRGFDTYFGYLLGSEDYYSHERCTLIDALNVTRCALDFRDGEEVAT GYKNMYSTNIFTKRAIALITNHPPEKPLFLYLALQSVHEPLQVPEEYLKPY DFIQDKNRHHYAGMVSLMDEAVGNVTAALKSSGLWNNTVFIFSTDNGGQTL AGGNNWPLRGRKWSLWEGGVRGVGFVASPLLKQKGVKNRELIHISDWLPTL VKLARGHTNGTKPLDGFDVWKTISEGSPSPRIELLHNIDPNFVDSSPCPRN SMAPAKDDSSLPEYSAFNTSVHAAIRHGNWKLLTGYPGCGYWFPPPSQYNV SEIPSSDPPTKTLWLFDIDRDPEERHDLSREYPHIVTKLLSRLQFYHKHSV PVYFPAQDPRCDPKATGVWGPWMDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for ARSB and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

ARSB-DNA

(SEQ ID NO: 51) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG AAATATTTATTAATTACAAGAAGAAAATAT TAACCTTACAATGAGGAAATGTTTACCTTAACAAAGTTATCCCATAAGAAAGCAATTCAGCATCATGT GCCTCTTAATAGGAAGCACCGAGAAACATACCACATCACTTTTTGTGGTATTCCTGCACAAATCCATA ACCTCTATCTAATTGTGAAGAAACATCAAACTCCAATTGAGAGATTTTATAAAATAACTAGCTTGTAC TGCACATTATGTGTTCAATACATAGATGGAAAATAGAATTAACTCTTCAATTTGCACATTTCCAGAGC ACTATTAACATATGCTTTTATTTTAAAAACATAGGACGTAAGAATCTGTGCAAGTTTAGCTAGTTTCA GGGGAAGTTGGTTAAAGGAGGAATTGTTCCTGCAGATTAGCACCCATCAATTATTTCTTCTTAATTTT TATCAAGGAGAATAGGAAGGATTACGGGGGAGAAAGACACAAAACCACAGCGGAAATTCTCAGTCCTT CAAGGTCTTCTACAGGGTGTTTAAATGAAAAGTTCAACCCTTGACATAATGAGTCAAACAGTTCTCTC AAAAGTTATTCTTTGAATTTAATGCTAAAATTTTCACTTTTTTCTGCTAAATTTCATTGATTCCACTA GAGATTAAAGTGCATACAACATAAACTAATCTACTTCATGCAAAGAAAAAAAGTGTATGTAAGAGGCA AACATTTCATGTGTTAAAGGATTCTTGGGGAAAAAAAGGTAAAATCATGACCCTCATACAAATATAAA AGTGAATACATGATTTTATTTAACTCATTAATAAGGAAATTGGTAAGGTGTTAAAACCAATTCAAAGG ACAATCCAAAGAACAGATCAGGAATACTAAAATAAATATGCAAGCGGAGGTGAAACTGTTTTCCTTGG TAGTGGTGGAGGGGAAGGATTGCTACTCCGCTGGATAAAGTTCATTTGTGTATATATAAATAAGAATT ATTTTCCATTGTTATTTATCTATAACTTATAAAGTTGTAAACAACTTCCACGGAATCAGACTCAACCT GGAAGGGTATGGTCTCTAGGCAATGCAAAAATTTTCCCCTACACCTGTTAACAACTATAATATCTCCA GACAGAGTAGACAGAAAGTCTGGATGGCAACGGGAATCTACTGGTCATACGGCTAACTTCCTAATTCA ATAAGCACGTGACTAAAGGATTTTTTCCTTCCACTCAGATATTTCAGGCTAACTAGATACTGTGTGCT TCTTAGTGTCACTGCTTAGTGGGGGAGCCAGCTCTGAGTGGGGTCATATCCGGACAAGCGAATGAGCT ATTTATTCAATGACCACGCAACACTCCAAATCCTCCCAGGGCAACTTGAAAGTAACCGCACCTTCCAA AGGGCACCGTGCAATCAGACTGTGTGTTTGGCCTCCTGTTTGCTAGTGGGGAGGAAGCGGCTTCATGG GTGTACACTACGCATAAATGAATGTGAAAGGCTATTTAGACCTCTGCCTTTTCACCGTCCTCCCACCT GCCACAGGCTGGGCTCTTGTGCTAGAAATGACTTGCTAGCTAGACATCATGGTTCAGGATCTGAGTCA GAGGTTTAACCATTTATAAGCTTTTTTCTTATGAAAAATTGGCACTAATTATAATGTCTAACTGTCAG AGTTGTTGCAGGCTTTACAGGAGACGCGGGCTGTGAAGATGCTTTGTAAATTGTGAAGCGTTATTAAA GAACACATCTTTTTTTTTTAGGAAACCACAGTGCAAATTTAATTGCCGGGGAAGATAACGGGCCTTGG TGCCCTCCAAGCGTCAGCTGAGTTTCCAAGAAGCCGGGCAGCGGGCGCCCGCGGGTTCGTCTCTGGCT CCTCCTCCGCCACAGCAGCCGGGGGCCCGGGTCGGAGGCGGCGGGGGCCGAGCGCCCGGCCTCGCAAG CCCACGGCCCGCTGGGGGTGCCGTCCCGCGCCGGGGCGGAGCAGGCCCCGGCAGCCCAGTTCCT

ATGGGCCCCCGGGGCGCAGCGAGCCTCCCCAGAGGGCCAGG ACCAAGGAGGCTCCTTTTGCCAGTCGTCTTGCCGCTTTTGCTCCTTTTGCTTCTCGCGCCACCCGGCA GTGGGGCAGGAGCTTCTCGCCCACCTCACCTTGTCTTCCTGCTTGCTGACGACCTTGGATGGAATGAT GTGGGTTTTCACGGTTCCCGGATTCGAACACCACACTTGGATGCTCTGGCTGCGGGGGGCGTACTGCT CGATAATTATTACACACAACCGTTGTGCACACCGTCTCGGAGTCAGCTTCTGACGGGACGATATCAAA TAAGGACTGGGCTGCAACATCAGATTATATGGCCATGTCAACCCAGTTGCGTGCCCCTTGACGAGAAA CTCCTGCCTCAGCTGTTGAAGGAGGCTGGATACACGACACATATGGTCGGCAAGTGGCATCTGGGAAT GTACAGGAAAGAGTGTCTCCCAACCCGGCGCGGATTCGATACGTATTTTGGGTACTTGTTGGGCTCAG AAGATTACTATTCACACGAAAGGTGCACTCTTATCGACGCACTCAACGTTACGCGCTGCGCACTTGAT TTCCGAGATGGAGAGGAAGTTGCAACTGGGTATAAGAATATGTATTCAACAAACATCTTTACTAAGCG GGCAATAGCCCTCATTACTAATCATCCCCCCGAAAAACCGCTGTTTCTCTATCTCGCCCTGCAGTCAG TCCATGAGCCGCTGCAGGTGCCTGAGGAGTACCTCAAACCATACGACTTCATACAAGATAAGAACCGA CACCATTATGCGGGTATGGTCTCTCTGATGGACGAGGCTGTCGGGAATGTTACTGCAGCATTGAAATC TTCCGGCCTTTGGAACAACACAGTCTTCATATTTTCTACGGACAATGGCGGGCAGACTCTTGCCGGTG GCAATAACTGGCCTCTTAGGGGTCGCAAGTGGTCCCTCTGGGAAGGAGGCGTCCGCGGTGTAGGGTTT GTAGCGAGCCCCCTCCTTAAACAAAAAGGAGTTAAAAACAGGGAACTTATTCACATTTCCGATTGGTT GCCCACGCTCGTCAAGCTCGCGAGGGGTCATACAAACGGGACAAAACCGCTTGACGGGTTTGATGTAT GGAAAACCATTTCTGAGGGGTCTCCTAGCCCCAGGATCGAGCTGTTGCATAACATAGACCCAAACTTT GTAGACTCCTCACCCTGTCCCCGAAATTCAATGGCCCCTGCCAAAGATGATTCATCCCTCCCTGAGTA CTCCGCTTTTAACACAAGCGTACATGCCGCTATTAGGCACGGCAATTGGAAGCTGCTGACCGGGTATC CTGGTTGTGGTTATTGGTTCCCTCCCCCCTCACAATACAACGTGTCTGAAATACCGAGTAGTGATCCG CCGACAAAAACCCTGTGGCTGTTCGATATTGATCGAGACCCTGAAGAACGCCACGATCTCTCCCGGGA ATACCCCCACATTGTCACCAAGCTTCTTTCACGATTGCAATTTTACCACAAGCATTCAGTACCCGTTT ACTTCCCCGCCCAGGACCCAAGGTGCGATCCTAAAGCAACGGGGGTTTGGGGACCATGGATGGACTAC AAAGATGATGACGATAAATAG

The GUSB protein sequence is:

(SEQ ID NO: 52) MARGSAVAWAALGPLLWGCALGLQGGMLYPQESPSRECKELDGLWSFRAD FSDNRRRGFEEQWYRRPLWESGPTVDMPVPSSFNDISQDWRLRHFVGWVW YEREVILPERWTQDLRTRVVLRIGSAHSYAIVWVNGVDTLEHEGGYLPFE ADISNLVQVGPLPSRLRITIAINNTLTPTTLPPGTIQYLTDTSKYPKGYF VQNTYFDFFNYAGLQRSVLLYTTPTTYIDDITVTTSVEQDSGLVNYQISV KGSNLFKLEVRLLDAENKVVANGTGTQGQLKVPGVSLWWPYLMHERPAYL YSLEVQLTAQTSLGPVSDFYTLPVGIRTVAVTKSQFLINGKPFYFHGVNK HEDADIRGKGFDWPLLVKDFNLLRWLGANAFRTSHYPYAEEVMQMCDRYG IVVIDECPGVGLALPQFFNNVSLHHHMQVMEEVVRRDKNHPAVVMWSVAN EPASHLESAGYYLKMVIAHTKSLDPSRPVTFVSNSNYAADKGAPYVDVIC LNSYYSWYHDYGHLELIQLQLATQFENWYKKYQKPIIQSEYGAETIAGFH QDPPLMFTEEYQKSLLEQYHLGLDQKRRKYVVGELIWNFADFMTEQSPTR VLGNKKGIFTRQRQPKSAAFLLRERYWKIANETRYPHSVAKSOCLENSLF TDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GUSB and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

GUSB-DNA

(SEQ ID NO: 53) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG TGCCCAGCTAAATATGGAGATGCGGTTTCT CCATATTGGTCAGGCTGGTCTCGAACTCCCAACCTCAGGTGATCTGCCTGCTTCAGCCTCCCAAAGTG CTGGGATGACAGGCGTGAGCCACCGCACCTGGCCAAGGCACTTGGTTTCTTAGATCACCCACTTGGCC CTCTTCCAAGTTGTACTTTCCTTCTTTCCTTCCTGTTCTAAAGTTTTTTAATATTTTTTTTTTTCCTG AAATGGCATCTCACTCTGTAGCCCAGGCTGGAGTGCGGTGGCGTGATCTCAGCTCACTGCAACCTCTG CCTCCTGGGTTAAAGCATTTCTCCTGCCTCAGCCTCCCAAATAGTAGGGATTACAGGTGCCTGCCACC ACGCCTGGCTAATTTTTGTATTTTTAGTAGAGATGGGGTTTCTCCACGTTGGCCAGGTTGGTCTCAAA CTCCTGATATCAAGTGATCCTCCCGCCTTGGCCTCCCAAAGTGCTGGAGTTTGGAGTTACAGGCCTGA ACCTCTGTGCCTGGCCTGCTTTTTTTTTTAGACTGAGTCTTGCTCTCTCGCCAGGCTGTAGTGCTGTG GTGCGATCTCGGCTGACTGCAACCTCTGCCTCCCGCGTTCAATCGATTCTCCTGCCTCAGCCTCCCGA GTAGCTGGGACTACGGGCGCATGCCACCATGCCCAGCTAATTTTTTAGTAGAGATGGGGTTTCATCAT ATTGGCCAGGCTGGTCTCAAACCCCTGACCTCGTGATCCCCCCACCTCCGCCTCCCAAAGTGCTGGGA TTACAGGTGTGAGCCACTACGCTCAGCACTGGCCTGCTTTTTAACAAGCTTTTACTACTGCTCTGCAG CTTACCTCCCTCTGGCTTTCTGCCTTATGCCCCTCAGTGCAATTCTTTCTTCTGAGGAGGCAAGAATT GAGGTTGTTGCTGATGTGTAGGGATTCACCACCCGGAACTCCACCAGTAACAGGTCGAGGATGCTAGT TGAAAATGTTATGTAAGCTGCATGCTTTTTACAAATGGTAGTGGTTCTCATGTCCAGCAATGGCCACT GCACCGTCCCTGTATGAAAGTCCCCTCCATAAATCTATGTCTCCTTTGCTGTCTCCAGATCTCCTCCT CTACCTCTCCCACACGGTGCCTTCCCTACTGGAGTAAACTGGGGTCCCGCAGGGCACCCTTTCCCTGC AATTTTTTTTTTTTTTTTGAGACAGAGTCTCGCTCTGTTGCCCAGGCTGGAGTGCAGTGGTGCGATCT CGGCTTACTGCAGCCTTTGCCTCCCGGGTTCAAGCGATTCTCCTACCTCAGCTTCCTGAGTAGCTGGG ATTACAGGCACGCACCATCACGCCCCGCTAATTCTTTTTTTTTTTTTTGTATGTTTACAAAATAGGGA CGGGGTTTCACTATCGTTGGCCAGGCTGGTCTCGAACTCCTGGCCTCAAGTGATCTGCCCCCCTCGGG TTCCCAAAGTGCACCTGGCCTCTCTCCCTGCATCTTTATGTGCCTGCAACACCAAGAGGGAGCTCTTG GCCCCTGGGTTAAGGTCAGGGCTCCAGAAGCCCAGGGTCAAGGCTATGGCCGCATCCCAAGGACGTGC ATCCCTGCAAGAGGCTGCATCAGACAGGCATGGAAGAGGCGCCGCTGGGGCCTCCTTGAATTCCTGCT GGGAAAAGCAAGTGGAGGTGCTCCTTGAAGAAACAGGGGGATCCCACCGATCTCAGGGGTTCTGTTCT GGCCTGCGGCCCTGGATCGTCCAGCCTGGGTCGGGGTGGGGAGCAGACCTCGCCCTTATCGGCTGGGG CTGAGGGTGAGGGTCCCGTTTCCCCAAAGGCCTAGCCTGGGGTTCCAGCCACAAGCCCTACCGGGCAG CGCCCGGCCCCGCCCCTCCAGGCCTGGCACTCGTCCTCAACCAAGATGGCGCGGATGGCTTCAGGCGC ATCACGACACCGGCGCGTCACGCGACCCGCCCTACGGGCACCTCCCGCGCTTTTCTTAGCGCCG

ATGGCGAGAGGCAGTGCAGTAGCCTGGGCTGCTTTGGGACC ATTGTTGTGGGGGTGCGCTCTCGGACTTCAGGGCGGTATGCTCTACCCTCAAGAGAGTCCCTCCAGGG AATGTAAGGAGTTGGACGGCCTCTGGTCCTTCAGAGCCGATTTCAGTGACAATCGCCGCAGAGGGTTC GAGGAGCAGTGGTACCGCCGACCGCTCTGGGAGTCAGGCCCAACCGTAGACATGCCAGTCCCATCTTC ATTCAATGACATAAGCCAGGACTGGAGGCTGCGACACTTCGTCGGGTGGGTATGGTATGAGCGCGAAG TGATCCTCCCTGAACGGTGGACTCAGGACTTGCGGACGAGGGTAGTACTTCGGATAGGTAGTGCTCAC TCCTATGCTATTGTCTGGGTGAACGGAGTGGATACTCTGGAGCATGAGGGTGGCTATCTTCCTTTTGA AGCTGACATCAGTAACCTGGTGCAAGTGGGGCCGCTGCCTTCCAGACTGCGAATCACCATCGCTATCA ATAATACTCTGACCCCCACTACGTTGCCGCCAGGCACCATCCAGTATTTGACCGACACCTCTAAATAC CCCAAGGGCTATTTTGTGCAAAACACTTACTTTGATTTCTTCAACTATGCCGGCCTGCAAAGATCTGT GCTGCTTTACACCACTCCGACGACCTATATAGATGACATAACCGTGACGACGAGTGTCGAACAAGACT CAGGTCTCGTCAACTACCAGATTAGTGTAAAAGGCAGTAATCTTTTTAAGCTCGAAGTGAGGCTTTTG GATGCTGAAAATAAGGTGGTGGCAAATGGAACGGGCACACAAGGCCAACTTAAAGTGCCGGGGGTAAG TCTGTGGTGGCCGTATCTTATGCATGAACGACCCGCTTATCTCTACAGTCTCGAAGTCCAATTGACGG CACAAACAAGTCTTGGTCCTGTGAGTGATTTCTATACGTTGCCTGTGGGCATAAGGACTGTAGCTGTG ACAAAGTCCCAATTTCTTATAAACGGTAAGCCCTTCTACTTTCATGGCGTCAACAAACATGAGGACGC TGATATTCGCGGAAAAGGGTTTGATTGGCCTCTCCTGGTCAAGGACTTCAACCTTCTCAGATGGTTGG GCGCGAACGCCTTTAGAACAAGCCACTATCCGTATGCAGAGGAGGTCATGCAAATGTGCGACAGATAT GGGATTGTTGTAATCGATGAATGTCCCGGCGTGGGCTTGGCGCTCCCCCAATTTTTTAATAACGTGTC TCTTCACCACCATATGCAAGTAATGGAGGAGGTAGTACGCCGCGACAAGAACCACCCCGCGGTAGTTA TGTGGTCAGTAGCGAATGAACCAGCTTCTCATCTGGAAAGTGCCGGTTACTACCTCAAGATGGTGATA GCCCATACAAAGTCTCTCGACCCTTCCCGCCCCGTGACATTCGTATCAAACAGCAATTATGCAGCCGA TAAAGGCGCCCCATACGTAGACGTTATATGTCTTAATAGCTATTACTCCTGGTATCACGACTACGGTC ATTTGGAACTCATTCAGCTGCAGCTCGCCACGCAATTCGAGAACTGGTACAAGAAATATCAGAAGCCA ATTATACAGAGTGAATATGGTGCTGAAACAATCGCTGGATTCCATCAAGACCCACCATTGATGTTTAC CGAGGAGTACCAGAAAAGTCTCCTCGAGCAATATCATCTTGGACTGGACCAAAAGCGACGAAAATACG TAGTAGGGGAACTTATTTGGAATTTTGCCGATTTTATGACGGAACAGAGCCCTACACGAGTTTTGGGG AACAAAAAGGGCATTTTCACCCGGCAACGGCAACCCAAGAGTGCCGCCTTCCTTCTTAGAGAAAGATA CTGGAAGATTGCTAACGAAACACGCTATCCCCACTCTGTTGCTAAGAGCCAATGCTTGGAAAACTCCT TGTTTACAGACTACAAGGATGATGACGATAAATA

The SLC19A3 protein sequence is:

(SEQ ID NO: 54) MDCYRTSLSSSWIYPTVILCLFGEFSMMRPSEPF LIPYLSGPDKNLTSAEITNEIFPVWTYSYLVLLL PVFVLTDYVRYKPVIILQGISFIITWLLLLFGQG VKTMQVVEFFYGMVTAAEVAYYAYIYSVVSPEHY QRVSGYCRSVTLAAYTAGSVLAQLLVSLANMSYF YLNVISLASVSVAFLFSLFLPMPKKSMFFHAKPS REIKKSSSVNPVLEETHEGEAPGCEEQKPTSEIL STSGKLNKGQLNSLKPSNVTVDVFVQWFQDLKEC YSSKRLFYWSLWWAFATAGFNQVLNYVQILWDYK APSQDSSIYNGAVEAIATFGGAVAAFAVGYVKVN WDLLGELALVVFSVVNAGSLFLMHYTANIWACYA GYLIFKSSYMLLITIAVFQIAVNLNVERYALVFG INTFIALVIQTIMTVIVVDQRGLNLPVSIQFLVY GSYFAVIAGIFLMRSMYITYSTKSQKDVQSPAPS ENPDVSHPEEESNIIMSTKLDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SLC19A3 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

SLC19A-DNA

(SEQ ID NO: 55) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCG CTATTACCATGCTATGCATGAATGAATGAATTCCTCAATAT CTCTCTCTGATTTAGACTGTGGCTATGAGATATTAGAGAATCAGAGTAAACTTCTCAAGGTCCAATTT GAACTCATTTTCTTCAAGAGGTGTGAAGGAAATCATGACACCTTCAGCCTTTAAGAAAATTTCACAAT ATTCTTTGGGAGGACCCAGCAATTTGCAAGGTTGCACAATGAGCAGGGCACTCCTACACCTAAGGTTC AGCTCAGGACTTTTCACAAATCATAGGAAGATGAAAATAGAAAACGCAGAGTCGTAGGACAGAGAACC AAGACACCTCGGGGTGTTTTAATCCATTTCACTTCCACTGGTAGCCCTTAGAAGCCACGCAGTGTTTA TCTTTAGGGAGGGTTTTTCAAGTCCACCAAGAGATGAACAGAAATAAAAATATTTTTTCCATTTTAAC CAATAAGAACCTTGTAATGCTTTAAAAAAATTCTCTGTTTAATAAGAAGTTTCACTTTAATATATAAA CTCTTTGCAGGCTAAGCGTAGTGGCTCATGCCTGTAATCCCAACACTTTGGGCGGGCAAGGCAGGAGG ATCCTTTGAGCCCAGGAGTTCAAGACCAGCCTGGGCAAGATAGTGAGACTCTGTCTCTACCAAAAAAA AAAAACAAAAAAATTAATGTGACGTGGTGGCACCCACCTGCAAGCCCAGCTACTTGGGAGGCTGAGGC AGGAGGATCAGTGTGCCTGGGAGATTGAGGTTGCAGTGAGCTGGGGTTGCACCACTGCACTCCAGCCT GGGAGATAAAGTGAGACTTTGTCAAAAAAAAAAAAAAAAGAAAGAAAGAAAGAGAAAAGAAAAGAAAA GAGGCCAGGTGGCCGGGTGCTGTGGCTCACACCTGTAATCCTAGCACTTTGGGAGGCCGAGGCGGGTG GATCACCTGAGGTCAGGAGTTTGAGACCAGCCTGGACAACATGGTGAAACCCCATCTCTACTAAAAAT ACAAAAATTAGCTGGGTGTGGTGACGGGCGCCTGTAATCCCAGCTACTAGGGAGGCTGAGGCAGAAGA ATTGCTGGAACCCGGGAGGTGGAGGTTGCAGTGAGCCAAGATCGTGCCATTGCACTCCAGCCCGGGGC CAACAACAGCGAGGCTCCATCTCAAAAAAAAAAAGAAAGAAAGAAAGAAAGAAAAAAGACCAGGCGCG GTGGCTCACGCCTGTAATCTCAGCACTTTGAGAGGCCGAGGCAGGCGGATCACGAGGCCAGGAGTTCG AGATGAGCCTGGCCAATATGGTGAAACCAAACCCCGTCTCTACTAAAAACACAAAAATTAACTGGGCG TTAATTTTTGGAGGCTGAGGCAGGAGAATCGCTTGAACCCGGGAGGCGGAGGGTTGTAGTGAGCCGAG ATCGCGCCACTGCACTCCATCCTGGGCGACAGAGGGAGACTCTGTCTCAAAAAAAAAAAAAAGAAAGA AAGAAAAGAGAAAAGAAAAGAAAAAGAAGAAGAAAAGAAAAAATTGTTTGTATCAGATTTTCAAAGTG CCAGGAAACCATCCCACTCTACCTCCTTTAAAAAAAAAAAGTGCAGAGTGATTATAACCACTGGCTCT GGAGCCAGGAGCCCCAACTAAAACCCAGGCTTCTCTATTTACTAGGCCTACTTCCTTCCGCCTCACTT TCTTCATGTGTAGAGTGGGGGTGACAGCCAGCCAGCCCTCTCTCCTAAGCTTTTGGAGAGAAATAAAT GGATTCATAAGAAAGGACATATTTGTAAATAAAGCAAACGATCGCTGTTGGATTCAGGCCCTCTTGCT TCATTATGCTGAATGTCAGTGTATTACTTAAGTTGTTCCTTTCAGCAGAGTTGACTGTTTCTGCCCAG AAAACCGGCCCTGGGCCAGGAAAATCTGGGCTTCCACACTGGGATGAAAGGTCTGGACGCCCGGATTC GCATATGCAAAGCGTGGGGGCGTGGCCCCGGGCTCCGGGCCAGGCAGGCTCCGCCCCCTTCCCACC

ATGGACTGTTACCGGACCTCACTCTCTAGCAGTTGGATC TACCCCACAGTCATCTTGTGCCTCTTTGGATTTTTCTCCATGATGCGGCCAAGCGAGCCGTTCCTTAT ACCATACCTTAGCGGACCCGACAAAAACCTTACGAGCGCGGAAATTACGAACGAGATCTTCCCGGTAT GGACCTACAGTTATCTTGTGCTTTTGTTGCCTGTCTTTGTCCTGACTGATTACGTTCGGTACAAGCCA GTTATAATACTGCAGGGGATTTCCTTCATCATTACCTGGTTGTTGCTGCTCTTTGGACAGGGCGTAAA AACTATGCAAGTAGTAGAGTTTTTCTACGGCATGGTTACCGCCGCAGAAGTGGCCTACTATGCCTACA TCTACAGTGTGGTAAGCCCAGAGCATTACCAAAGAGTGAGTGGATATTGTAGATCAGTTACCCTTGCC GCCTACACCGCGGGTTCCGTCTTGGCGCAGCTCCTGGTCTCACTTGCCAATATGTCCTACTTCTATCT TAACGTTATTAGCCTCGCCTCCGTTAGCGTCGCCTTTTTGTTTTCCTTGTTTCTGCCAATGCCGAAAA AAAGTATGTTTTTTCACGCAAAACCAAGTAGGGAGATCAAGAAGAGCAGCTCTGTTAATCCCGTTCTG GAAGAGACACACGAGGGAGAGGCTCCAGGCTGCGAAGAACAGAAACCTACCAGCGAGATACTGTCTAC ATCAGGAAAGTTGAACAAGGGACAGTTGAACTCACTCAAGCCAAGTAACGTCACAGTTGATGTGTTTG TGCAATGGTTCCAGGATCTCAAAGAATGTTACAGTTCAAAAAGACTTTTTTACTGGAGCTTGTGGTGG GCATTCGCAACCGCCGGTTTCAATCAAGTGCTTAACTATGTTCAAATCCTTTGGGATTACAAAGCCCC AAGTCAGGACTCATCCATCTATAACGGCGCAGTCGAGGCGATTGCTACATTCGGAGGCGCTGTTGCAG CGTTCGCCGTGGGCTACGTCAAGGTCAACTGGGATTTGCTGGGTGAGCTGGCTCTCGTGGTATTCTCC GTCGTGAACGCAGGATCTCTTTTCTTGATGCACTACACTGCAAACATCTGGGCGTGCTACGCCGGGTA CCTTATCTTTAAATCCAGTTACATGCTTCTCATCACTATCGCGGTTTTCCAGATTGCGGTAAATCTCA ATGTCGAACGATACGCGCTCGTATTCGGCATAAATACTTTCATAGCGTTGGTTATTCAGACAATAATG ACGGTGATCGTTGTAGATCAAAGAGGGCTGAACCTCCCCGTGTCCATTCAGTTCCTGGTGTATGGTAG CTACTTCGCTGTTATAGCTGGAATATTCCTTATGCGCTCAATGTACATTACATACAGCACCAAATCCC AGAAAGATGTGCAGTCTCCGGCTCCGTCTGAAAACCCCGACGTCAGTCATCCGGAGGAGGAGTCTAAC ATCATAATGTCAACGAAACTTGATTATAAGGATGACGATGATAAATA

The PLP1 protein sequence is:

(SEQ ID NO: 56) MGLLECCARCLVGAPFASLVATGLCFFGVALFCG CGHEALTGTEKLIETYFSKNYQDYEYLINVIHAE QYVIYGTASFFFLYGALLLAEGFYTTGAVRQIFG DYKTTICGKGLSATVTGGQKGRGSRGQHQAHSLE RVCHCLGKWLGHPDKFVGITYALTVVWLLVFACS AVPVYIYFNTWTTCQSIAFPSKTSASIGSLCADA RMYGVLPWNAFPGKVCGSNLLSICKTAEFQMTFH LFIAAFVGAAATLVSLLTFMIAATYNFAVLKLMG RGTKFDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for PLP1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

PLP1-DNA

(SEQ ID NO: 57) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG GGAGTTGGGAACCTTAAGGCACTGGGATGA GTGAGACACGGTCACCTGGCTGGGTCCCTTTTCTGGCCCTGGGCATAAGAACAAGCATAAGAACAAGG CGAAGACAGGGAATGTGGAGAGAGAAAAAGGAAACAGAGACAGACACATAGAGAGAAACAGAGACAGA GACAGGTAACAGAGACAAAGAGATTGAGACTTGGGGAGAGGATAGAATGAATATTAAGGCAATGGAGA TGGAAGAAAGGAGAAGAGAAATGTGTGTTAAGGGAATGTGGTTGATAAATTGGTATCTGTGGGTTTAT TGGGAACACATATTTTCTTTCCAGTAGAGTTGCTGTCCCCAGAGCTGCTGCTGAGAACTCAGGGGAAG CTTTGTGAGAGGGCTCAGTCTGAGTGATGTCCCCTGTGTGGAGAGCTGTCTCATCTATTCGAGCTGTG AAGGATCATTTGCCTCATCCTCTAAATCTGAACTCCCAAAGTTTGGGCTCACTCCTGCCATCTGATGA GCTGAGGAGACACATTTGGCGATTTCTTGCTCTTGGTCCTCCCCCTTCTCCAGGGCCATTCCGACAGT GACCATCCAGAAGTTTATTGCTGGCTCAATCCTACAGTTGAGCTTCCAAAGCAGGCATAGTCTGTGGC TGGCGAGCAGGGCTGGGGAGGGCGAGGGGCTCTAGGACCCTTTTCCATCAGTCACATGGCCTTAGTCT CGTCTGCTCTGGAAAGCTACTATTATACCGTTTTGCAAGGGGCAGCATTTCCAGAGATCCTTTTTTCT TGGGGCTGATACAAGAGCAAAGGATCTAGAGTTCTAGTACTCTAAGCAAGCCTCAAACGGTGCAGGAT TTGGCCCCAGTGGGCCCACAGGGGCATCTGCCAAAGACTCGTCCATTTCCTAACAGCAGAGCCCAAGC CAGTAACATGTCCAAAGTCACAGCCCAAAGAGAAAACTGTAAGACACAATCTTGCCTTTCTCCCACCC CAGGAAGGTACTAGTCTCTGCTCAGTATCTCCCTCCTCTTCTCTCCTCTCCCAAGGCAAAATCACAGG AAAAGTTCCAGGAGACCATACCTTCCTTCTCCGGAGTCTTCCAACAGGTGCCCCTCTTATTATATGCC AGCCAGTTGTTTTAAAGGCCATCCATGGGAGGACACCGGCCTCTAGGTCAAGGGAGCTGTGAAGGGAG ACAGGACTGACAAGGAGCCCAGACAGACACTGTTTAAGATTCACCTGTTCTAGAAAACCTTCCCAGGC TGATCCCATCTAGCAGTGGGCATTTAAATACCTTCACAGTCTTTAGAAATAGCTTATTGCTAAGGCAG GTTTTATATAGTATTTCCCTGTTTTTGCTGCTTAGCCATTTTTGTCTTACCGCTTCTTTCTCTGTGGC AAGGACTATATTTCGTTTCTTCTCTCCACCCTCACTGCCACCTGCTGCTTCACTCTAACCCACTCCCT GCCTCTTGTCTGCCTGGCTTAAGCTCTCTGATGAAGATATTACACTCTCAGGATAGAATACTGACTAC CTGATTCCCAGATCGTGTTCTTGACTTGTCTCGAAGTCGATTATCCTTCTTGGAAATCACCCACATCT TCAACGCTGGCCTTTTCTTTAACCTAGTCTGTGAACTTGCATAGGTCTTGCCCACTTCTGGGTCTTTA TTATTGTAGCTATAAAATTATTACAATTCTAGCCTCCCCCAGCCTAATCACAATCTGTTCATCGAATT GACAGCCTGCATTTTGTCTTCATGCAGTTGAAACTGAGAAGGATTTGGAGGAAATTATCTTAAAAGAC AATTTTTTCTTCTCTATTGTGTTCGTAGAGCTGGGGGTGGGGGTGGGGGAGGAACGCTTATTTTCCAA GGAATCGGGAGGGGAAAGGTGGAGAGGGCCAAGGGCAGCTAGGAGTGATGTGGGGAGCTGGAGCAGAT TCGGAAGGACTTTGGGAGCTAATATCTAGGTTTTTGACTCTGAGCCCCTGTTGGGGCTCTCACTTCAT GGCTTCTCACGCTTGTGCTGCATATCCCACACCAATTAGACCCAAGGATCAGTTGGAAGTTTCCAGGA CATCTTCATTTTATTTCCACCCTCAATCCACATTTCCAGATGTCTCTGCAGCAAAGCGAAATTCCAGG CAAGCCTTAGGGAAAAAAGGAAAAACAAAGAAAATGAAACAATTGGCAGTGAAAGGCAGAAAGAGAAG ATGGAGCCCTTAGAGAAGGGAGTATCCCTGAGTAGGTGGGGAAAAGGGGAGGAGAAGGGAGGAGGAGA GGAGGAGGAAAGCAGGCCTGTCCCTTTAAGGGGGTTGGCTGTCAATCAGAAAGC

TGGGTCTCCTTGAATGCTGTGCTCGATGTCTCGTAGGAGCGCCGTTCGCC TCTCTCGTCGCCACCGGATTGTGTTTTTTCGGTGTTGCGCTCTTTTGCGGCTGTGGTCACGAAGCTCT TACAGGTACGGAGAAACTCATTGAGACTTATTTCAGTAAGAATTATCAAGATTATGAGTATCTGATAA ATGTAATTCATGCATTCCAGTATGTTATTTACGGAACGGCTTCTTTCTTTTTCCTGTATGGAGCCCTT CTCCTGGCTGAGGGTTTCTATACAACAGGTGCAGTGCGCCAAATCTTTGGCGATTATAAAACTACTAT ATGTGGAAAGGGGTTGTCCGCGACCGTTACAGGCGGCCAAAAGGGTCGGGGTAGCAGAGGTCAACACC AGGCACACAGTCTGGAGCGAGTATGCCACTGTCTCGGAAAGTGGTTGGGTCACCCAGATAAATTTGTA GGGATTACTTACGCTTTGACGGTTGTATGGTTGCTGGTTTTCGCGTGCTCAGCTGTACCCGTTTACAT CTATTTTAATACCTGGACGACCTGTCAGTCTATAGCGTTCCCAAGTAAGACCTCTGCATCAATCGGTA GTCTGTGTGCCGACGCGAGGATGTATGGCGTGCTGCCATGGAATGCTTTTCCAGGGAAGGTGTGTGGG AGCAACCTCCTTAGTATATGTAAAACTGCCGAGTTTCAAATGACGTTTCACTTGTTCATAGCGGCGTT CGTGGGAGCAGCAGCAACCCTGGTATCTCTCCTCACATTTATGATCGCTGCTACGTACAACTTTGCAG TACTGAAACTTATGGGACGGGGCACTAAATTCGACTACAAGGACGACGACGATAAATA

The TPP1/CLN2 protein sequence is:

(SEQ ID NO: 58) MGLQACLLGLFALILSGKCSYSPEPDQRRTLPPG WVSLGRADPEEELSLTFALRQQNVERLSELVQAV SDPSSPQYGKYLTLENVADLVRPSPLTLHTVQKW LLAAGAQKCHSVITQDFLTCWLSIRQAELLLPGA EFHHYVGGPTETHVVRSPHPYQLPQALAPHVDFV GGLHRFPPTSSLRQRPEPQVTGTVGLHLGVTPSV IRKRYNLTSQDVGSGTSNNSQACAQFLEQYFHDS DLAQFMRLFGGNFAHQASVARVVGQQGRGRAGIE ASLDVQYLMSAGANISTWVYSSPGRHEGQEPFLQ WLMLLSNESALPHVHTVSYGDDEDSLSSAYIQRV NTELMKAAARGLTLLFASGDSGAGCWSVSGRHQF RPTFPASSPYVTTVGGTSFQEPFLITNEIVDYIS GGGFSNVFPRPSYQEEAVTKFLSSSPHLPPSSYF NASGRAYPDVAALSDGYWVVSNRVPIPWVSGTSA STPVFGGILSLINEHRILSGRPPLGFLNPRLYQQ HGAGLFDVTRGCHESCLDEEVEGQGFCSGPGWDP VIGWGTPNFPALLKTLLNPDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for TPP1/CLN2 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

TPP1-DNA

(SEQ ID NO: 59) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG CTCCTTTGGGTTCCACTGACACCCCTGCCC CTGCCCCTGCCCAGAACCAAGTGCCATTTCTCACTCTGGAGCCTTAATAAACTGCAATTTGTATCCAG TCTCCAGCTTTGTTCTATAGGGATGACTGGAAGACACCTGGCAGAGTATTGTGGATACCTCAGGAGGC ACAGAGGGGTGGTGGGGTGGGGATGGCACTGGGAGCTCAGGAGCCTAGCCTGAGGCTGATGATCACAT CTCTCTGCAGCTATTCTTTTCCCTCTAATATGGGCAAAGAGGCCAGCAGGGCCTTGAGAGGGATCAGT TGGGTGGGAGAGGGGATCTTGGGGATGAGCAGCTCTGGGCCCGAAGTTCTTAAAATAAGTTGGGGTGG GTACAAGAGCAGTCAAGTGGTTTATTTGTTCTTCTTGGGGGCCACTAAAAATCCACATTGTAAAAAGA GCTCAATTTGTTGAGCCTTTGTCATGTCAGGCTCTCTGCAGGTGGCTGCCTTGCTTAATCTCAGTGTA AATTTTCACAGTCATACAAAGGGATTTGGGAACCACTGGTGTTGCCTGTTCTTTGGGGAGCCAGGCTG TGAGGGAAAGGCAATTGGCCAGTGTTTGAGAAGTTCATGAGATTGAGGAAATTAGAAAAAAAAAAAAA AGTTGTGGTCAAAGGGAAATGTTTCTGAGCATGATGCTAGTAAATACAGCTCTAGGATCCACGCTTAG TGGGAAACTGGAGGGATCAATGGACAGAGAGAAGTCAGATTAATAGGAGTGAGGAAAAACAATGGCTT GAAAAAACAGAAGGTTATAGTCTAAGAAAGCATTCTATAATTATAATTTCAAAGGTAGAGCAGTTTTG AGAGATAGCAAGCCCAATGCAGCCATGGGACTGGTTTGCTTAAGTGAAGTGAAGGTAATGCTCACTGG GTTTAATGAGATGAAGAAATGGAAGGTTAGGGTGTTGAATGGGTCTTTTACCTAGATATTTTGATCAT CTAGGTCAAATGATCGCAGGAGTTGGGATGGACAGAAAGGTGAAGTGCCATAATCTTCAGTGTGGGAA TATAATCTATAGGTTAATGGAAGCCAGTGGCCTGTAGGACAACAGCAGGAGTAGAGGGATCTATCTAA AAAGTATTGAGGTCAGAACAAGGGATTTCACATGAGTATTGGATTAATGGTTTTGGAAGTTAAAATGA CACTGCTGACACCATCTTCCATATGGATTTTTGGGGGGAAAAAAAGGAAGACTGGAAGGGAATTGAAT CCTCAGGGTTTTAACTCTCATTGAAAATCCTCTTGTAATGACCCCAGTTGGAAGTAGTAAACTCAGAC CTCCTTGTGGGCTTTGAGTTACCATTAGAAGAAGCAAAGGTCCGTTTCCATTTTATCCACCTGAGCCC ACTAAACAAGATGCAAGATTCCTCCATGGCCCTTAGAACAAAGTTGATTTCCTTGAAAACCTTGGGAA CCCATAATAAACAGGACCCCAGCTGATTGTAGATCTCCTGGGAAGCTACTTAAAACTGGAAACTGATT TGAATAAAAGGATCCTGGTCTTGCAAAAGCTTTACTCTGTTCATAAATGTAGTCGTAAAATGAAGACA AAATTGATAATATGGGGACATAAAGGATAAAAGAGGAAAAAAATTTTTTCACTGCAATCTTTCGAGGC AGATCACTTTTATATAAGTCTCCATATTGTAAATGCAGAAACCTAGGCTCTGAGAGGTTATTTTGCTG ATGTCATACAGCTAGGAAGAACCCCAGTCTGTGGGTCTCTACAGCCCACTCACTTGTGGTGATTCCCA GGGGACCAGGCTCAGGACGCAGGTGGGGAGCCCTGGGCTTACTCAGTGCTTGACTGGCCAGAGGGGAG AATCCGGGTGGCGGCCCCACCCTTGCCTAGCATTTGGGACCACCCATGCAAGGGAGGAGCCAGTACCG TCACTAGTTACTAGGCAGAGGGGTAGTGGTGGTGGAATATAGAGCTCATGTGATCCGTCACATGAC

ATGGGCTTGCAAGCGTGCCTGTTGGGGCTCTTCGCATTG ATTTTGAGTGGAAAGTGTTCCTACTCACCCGAGCCCGACCAGCGCCGCACACTCCCTCCTGGATGGGT AAGCCTTGGCCGGGCCGATCCAGAAGAAGAGCTTAGTCTTACTTTTGCATTGCGACAACAGAATGTCG AAAGGCTTTCCGAACTGGTACAAGCTGTGTCAGATCCGTCTTCACCTCAGTATGGTAAATACTTGACT CTCGAAAACGTCGCAGATCTCGTACGCCCGTCTCCCCTTACTTTGCATACTGTTCAGAAGTGGCTGCT TGCGGCTGGTGCTCAAAAGTGCCACTCCGTGATAACTCAAGATTTTCTGACCTGTTGGCTTAGCATCC GGCAAGCAGAATTGCTCCTGCCCGGAGCGGAGTTCCACCACTATGTCGGTGGTCCTACAGAGACGCAC GTGGTGAGATCACCTCACCCCTACCAGTTGCCACAAGCGTTGGCCCCTCATGTCGACTTTGTAGGAGG ACTCCATAGGTTTCCCCCAACTTCAAGTTTGCGCCAGCGGCCAGAACCACAAGTCACTGGTACAGTTG GACTGCATTTGGGAGTCACCCCCAGCGTCATACGCAAAAGATACAACCTTACTTCACAAGATGTCGGC TCCGGGACGTCCAATAACTCTCAGGCATGCGCGCAGTTCCTGGAGCAGTACTTTCATGACTCCGATTT GGCGCAATTTATGAGGCTTTTCGGAGGTAATTTTGCTCACCAAGCCTCTGTAGCAAGGGTCGTTGGTC AACAAGGACGGGGGCGGGCTGGCATCGAAGCAAGTCTTGATGTACAATACCTGATGTCAGCGGGAGCT AATATTTCTACGTGGGTTTATAGCTCCCCCGGCCGCCATGAGGGTCAGGAACCGTTTCTTCAATGGCT GATGTTGTTGAGCAATGAGAGCGCGCTTCCTCATGTCCACACGGTCTCCTACGGAGATGACGAAGATA GCCTGTCATCCGCATACATACAACGGGTCAACACAGAACTCATGAAAGCCGCGGCCAGGGGCCTCACC TTGTTGTTTGCTTCTGGAGATAGCGGAGCCGGCTGCTGGTCTGTGTCTGGGCGACATCAATTCAGGCC AACATTCCCGGCGTCCAGTCCCTATGTCACTACCGTGGGGGGCACCTCCTTTCAAGAGCCGTTCCTCA TAACCAACGAAATTGTCGACTACATTAGTGGAGGCGGCTTCTCAAATGTGTTCCCCCGGCCGTCATAC CAGGAGGAGGCAGTTACAAAATTCCTCTCTAGTAGCCCGCATTTGCCTCCATCCAGCTACTTCAATGC AAGTGGGCGCGCGTATCCCGATGTAGCAGCCCTTTCAGACGGCTATTGGGTAGTCAGTAATCGCGTCC CCATACCCTGGGTTTCTGGCACTTCCGCCTCAACGCCTGTGTTCGGGGGCATATTGTCACTGATAAAC GAACACAGGATATTGTCCGGCAGGCCGCCCTTGGGATTTTTGAACCCTAGATTGTATCAACAACACGG GGCGGGTTTGTTCGACGTAACCCGAGGCTGCCATGAGTCTTGCTTGGACGAAGAGGTAGAAGGTCAAG GGTTCTGTAGTGGGCCAGGCTGGGACCCTGTAACTGGATGGGGCACCCCGAACTTTCCCGCTCTGCTT AAAACGCTTCTCAACCCTGACTATAAGGATGACGACGACAAGTA

The ACY2/ASPA protein sequence is:

(SEQ ID NO: 60) MTSCHIAEEHIQKVAIFGGTHGNELTGVFLVKHW LENGAEIQRTGLEVKPFITNPRAVKKCTRYIDCD LNRIFDLENLGKKMSEDLPYEVRRAQEINHLFGP KDSEDSYDIIFDLHNTTSNMGCTLILEDSRNNFL IQMFHYIKTSLAPLPCYVYLIEHPSLKYATTRSI AKYPVGIEVGPQPQGVLRADILDQMRKMIKHALD FIHHFNEGKEFPPCAIEVYKIIEKVDYPRDENGE IAAIIHPNLQDQDWKPLHPGDPMFLTLDGKTIPL GGDCTVYPVFVNEAAYYEKKEAFAKTTKLTLNAK SIRCCLHDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for ACY2/ASPA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

ACY2/ASPA-DNA

(SEQ ID NO: 61) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG TTTTTTGGGTCATCCCAAAAATCAAGTACA CTTTGGGAAACAGGGAGTTAAAAATCTTTCGGAAGTTAACTTGGTATAAGAGTATGAAAAGCCTCTGT TGCTCTACTTCTGAGGAAATGCTCTCCTTTTTCCTAATAAAGCTTTCCACAGAAGACAAACTCTGTAC ACAAAAAACAAGGTAAGTATGGGAAATAATTGCTGCAATTCATTAACTCTCAAAAAAGTTATTCATTT TGACATGTAAGAGAAACTTTATTTATGAATGTGAAATGTGCTTCAAAGTGCTGATCTGTTAAAATTCC ATAAAACAAGCTTCAAAATGCAAGTCATTTGTGCCAGCTACGAGTAAATAACTGAAGCAGCATTTCCA GAGAGACTAGGGCAAAGGACAGAACAAACTACAAATCAGCAGAAAAGAAACCAAGCATAGTAGAGTGT TAATAATTCACCATGGTTACTGCTCTTAAAACCAAAGCAACTAAACAACTGTCATCTGTTTACTTTTA CGTGTGTTTTCATCATCTCTACACCGTCTGAAGTGTTCAGTGTACATGGATGTGGACAGACAGTCAAA GCCTACAGGAGCTTTTTTTTTCTATTAGAACAGTCATTTTAATGCATAGATTTGATGTGGTTATTTTG CTTTCTCTATCTCTGCATTATAAGCTCTTAAAGGAAGAACATTCAGTGGGTTTATTAAATATTAGGAA GCATTCATATTTTATTTTTCCACCATGTATTTGGTTTGTATGCATGTTTGTTTCCTGAGCACACTGTA ATGGCTGTTTATGTGAATTCTGAAAGAGCAAAACTAGAACTGTGAAGAAGACCAAAAATAACAGAGAG GCACCCTATTGTCCTGTGAAAAACACTAGACTTGGGATGAGAAACATGGGTCTCAGGCCTAGGTTCTC CTACATCCCTGCAGAACCTTAACTGAGTTACTTAACCTCTCTTTCGTTTACCCCTGCAGTGGGGATGT CAACACCTAACCCACCCTATCGTATAAAATTAATGTATGAATAAACTGAGTGAAAGGACATTATAAAT TAAACTCTGCAATTGTAATAAATTACTCTTATTGTACCCTCTATCAAACAACCTGGCGTTACTAGTAC ATGGTATTCCCAGTACTTGAACATATGTGACTTTCTGGGTGACTGAGCATGAAATCAAATCAGATTTG GCTCAGAGTCATTTCTCCAAAGGGATGTAATCATCTTAGTATTCTGGAAAATTTCCCCTAATAAGACC CCTTTTTGAGTAACACAGTCCAGTGGAGAGTCCCCGCTGACAGTGAATAAGGCTGTGTCTATGTAAGT TCACATGATGTGGTTAGCACATGCAGTGTGTCCCAAGACATTTTCAGGCATCACAAAAACTTGAAAAG TACTAACAGTTGTCTTTCCTTTGGTATTTAGGCAAAAAATGAGGAAGATTCATAAGTAAGTTAACACA GAATTACCAAAAACCTCATGAGAAAGAAATGAAGGGATGTTTCAGGGTAGCTTTTCGAGTCCCAAGTG ATCATTGATTTGGCCCTTCTGTTTCTGATTGTGAAAAAGCATTCTGAAAGAATGGGCGCCGGTTCAAG AGGAGGTCTCTGAGGGTCAGCCTTTGGCTGTTTATAGAGGTGAGATTCAAATGCCCTCAGATCATGAA AAGTGCTTGAACTCATTTCAGAGAAGAAATGTTTTGAAATGCCCGTGGAAATACTGAGTGGGCCACTT TTTTATTTTGTGAAATTAGAAACGTATAAACTATTTTTATTATTACAGATAATTGTGAAAGCCTCACT GGATGACATCCTAGCTGAGGAAAAGAATGGAATTTTTGTATTAGTATGAAATGCTAATTTATTACTGT ATTTAGATCTACTGACCATCTGAGGGAGTTAGAAGTTAAAGTAAACAGCTGTATCTCTAGTTGATCTT TGCATATTTTAATCCAAATATGGCAAAGGGCAGGGCTAAAGAAGGGAGTGTCCATAAACGGGGCTC

ATGACAAGTTGTCACATAGCTGAGGAACACATCCAGAAG GTTGCTATTTTTGGCGGCACTCACGGTAACGAACTGACAGGGGTCTTCCTCGTCAAGCACTGGCTTGA GAATGGGGCTGAAATTCAGCGAACAGGACTTGAAGTAAAACCGTTTATAACGAACCCACGCGCTGTAA AAAAGTGCACGCGATATATCGATTGCGACCTTAACCGGATATTTGATCTGGAGAATCTTGGGAAGAAA ATGTCAGAGGACCTCCCTTATGAGGTGAGACGAGCGCAGGAGATTAACCACCTCTTTGGTCCCAAGGA TTCCGAAGACTCCTACGATATAATTTTCGATCTCCACAACACGACCTCTAACATGGGTTGTACCTTGA TCCTCGAGGATAGTCGCAACAATTTCTTGATTCAAATGTTCCACTACATAAAAACATCTCTCGCTCCC CTTCCTTGCTACGTATACCTCATTGAGCATCCAAGTCTTAAGTACGCAACCACCCGGAGCATAGCGAA GTATCCAGTGGGAATTGAAGTCGGGCCTCAACCCCAGGGAGTTTTGCGGGCGGACATCCTCGACCAGA TGAGGAAAATGATTAAGCACGCGCTGGACTTCATACACCATTTTAATGAAGGGAAAGAGTTCCCGCCA TGTGCCATAGAGGTTTATAAGATTATTGAGAAGGTAGATTACCCTAGGGACGAGAATGGGGAAATCGC TGCCATCATACACCCCAATCTCCAGGACCAAGATTGGAAGCCACTTCATCCCGGCGACCCAATGTTCT TGACGCTGGACGGCAAAACGATTCCCCTTGGGGGTGATTGCACGGTATATCCAGTGTTTGTGAACGAG GCTGCTTATTACGAAAAGAAAGAAGCATTCGCCAAAACCACGAAATTGACACTGAATGCAAAATCTAT CAGATGCTGTCTCCACGACTACAAGGATGACGATGATAAATA

The MANBA protein sequence is:

(SEQ ID NO: 62) MRLHLLLLLALCGAGTTAAELSYSLRGNWSICNG NGSLELPGAVPGCVHSALFQQGLIQDSYYRFNDL NYRWVSLDNWTYSKEFKIPFEISKWQKVNLILEG VDTVSKILFNEVTIGETDNMFNRYSFDITNVVRD VNSIELRFQSAVLYAAQQSKAHTRYQVPPDCPPL VQKGECHVNFVRKEQCSFSWDWGPSFPTQGIWKD VRIEAYNICHLNYFTFSPIYDKSAQEWNLEIEST FDVVSSKPVGGQVIVAIPKLQTQQTYSIELQPGK RIVELFVNISKNITVETWWPHGHGNQTGYNMTVL FELDGGLNIEKSAKVYFRTVELIEEPIKGSPGLS FYFKINGFPIFLKGSNWIPADSFQDRVTSELLRL LLQSVVDANMNTLRVWGGGIYEQDEFYELCDELG IMVWQDFMFACALYPTDQGFLDSVTAEVAYQIKR LKSHPSIIIWSGNNENEEALMMNWYHISFTDRPI YIKDYVTLYVKNIRELVLAGDKSRPFITSSPTNG AETVAEAWVSQNPNSNYFGDVHFYDYISDCWNWK VFPKARFASEYGYQSWPSFSTLEKVSSTEDWSFN SKFSLHRQHHEGGNKQMLYQAGLHFKLPQSTDPL RTFKDTIYLTQVMQAQCVKTETEFYRRSRSEIVD QQGHTMGALYWQLNDIWQAPSWASLEYGGKWKML HYFAQNFFAPLLPVGFENENTFYIYGVSDLHSDY SMTLSVRVHTWSSLEPVCSRVTERFVMKGGEAVC LYEEPVSELLRRCGNCTRESCVVSFYLSADHELL SPTNYHFLSSPKEAVGLCKAQITAIISQQGDIFV FDLETSAVAPFVWLDVGSIPGRFSDNGFLMTEKT RTILFYPWEPTSKNELEQSFHVTSLTDIYDYKDD DDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for MANBA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

MANBA-DNA

(SEQ ID NO: 63) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG GATTATTCTTTGATGTTCTCTGTTGTCAAA GTGAAGTAACCTAAATGATGTTATGCTTGCATCCTGGAATGAAAGGAGGAATGAGAATCTTCTATTAT TGTTTTTCTAAAAATTATATTTCTTAATAAACAGAATATATCCATATGTATCATCAAGGATGAATTTT CCTCTGATTTGGCTTAATGAAATCTCTGGGAATTATGAAAAAATTCCTTTGCCGCTCTTGTTGCCATA AACCTTGTGTTATCAGTGTTGCACAGACCATGGCTAGCCATTTAATGCCGTGAATTATGGCATATAAT TTGAATTGAGAGCTTTGTTTCTATCAAAGGTAAAAATGCTTCTGGAGTGAGTGAGGAAGGCTTTGAAG CAGTGAGAGCGTTTCCCCTATAGCATCATTGGGCTCTGACAGTAGGACCTTGAAGAGGAGGGTTCTAA TCCTGTCTGCCACTATGTGACAGGCAAGTCACCTGATCTTTTTTTTTTTTTTTTTTTTAGAGTCTTTC TCTATAGCCCAGGCTGGAGTGCAGTAGTGCCATCTCGGCTTACTGCAACCTCTGCTTCCTGGGTTCAA GCGGTTCTCCTGCCTCAGTTTCCCGAGCACCTGCGACTACAGGCACGTGCCACCACGCGCCCAGCTAA TTTTTGTATTTTTAATAGAGACAGGGTTTCACCATGTTGGCCAGGCTGGCCTCGAACTCCTGACCTCA AGTGATCCACCCGCCTCGGCCTCCCAGAAGTGCTGGGATTACAGACGTGAGCCACCGCGCCTGGCCCC GATCTCTTTGAACTCAGTTCCCTCATCTGTAAAGCCAGCGGCTTGGGTTGGATAATCCATACTGTCCT TTAAGCCAAGATATTCAGGGCTTGTAAATAATGCTGACTTTGCAAAGTAAGATATTGCCCGGTGTCTG CAGAATCAGGCAATTCCAAGGCCATTGTAAGGCGAAACAAAGCTCAGATTTGATGAGAGAAAATTTCT TTTCAAGGACTTCTTCCGAAGCATAAATATACGGCAGATAGCGTCAACACAGGAGAAAGGCAGTCTAT TTTATGCAATGTAAAATTCCGTCTTAACTTCTAGGATTACTGTTACATCCTATTGCAAAAATGGGACT CAGGTAGACCATTTGACTACAAGACCCGAAATAAGTCAGTGGTATTTCTTGGGTACTCTGGCATTGTT AGGGACGATCACATATGTTTACTCATTTTATACTTATAACACCTTGAAAACTTCAAGAAACGGAGATG GAGATTTTGCGGCTTGCCCAGGTCCCACAGCTAGTGAGTGCAGAGGATTTTAAACTCAGCTGCGCGCC TAGTGCAGGTTCCAGAACCTCAGAAACCTCCGTGGGGCTTTATGAAACATAAGGACGCAGGCCGCTAG TAACAATAGCTAACGTGAATGCCTTCTCTGGGCCAGGCTCCATGCTGCATGCTATAGTCGCATTTTCT TGGTTAGCCCTCAGAACAACCTTCTGATGGAGATACTGCTAGTACTTGTTTACTCTTTGAAGGGCGGG GTAGGCTCTGAGACCCGCGAGTTGAGCTGCAGCGGGGTGAGTGTTACGCTACCAGGTAGACGAGGGTC TGTGTAAATTTGGCGGAAGGGAAGTGGTGGGTTGTCTCCCAGTTTGGGTTCTCTGAAGGAGTGAGGGG ACTCTCCAGCTATGGTCTCCACGTACAGTCGGTCTCTGATCTCCCGAGGCTTTGTGCCACTGCGCGCC CAGGGATCTTTCTGTCCCAATTACCGTGCAAGATTCTTGCCTCCAGTTGTATGTACTGAGGCGGCGGG AAGAAGCGCCGAGGGAAGGCTCAGACCGCAATGCCCCCCAGCCTGTAGCTATTCTCGGGGGCTGCAGC TCCCGCACCCGCGACGCCCGGCTTTCAGCGGGTGCAGGCGCAGCCTCCTCGTTCCCCTCCCGCCCGCG GCTGCGCCCGGAGAGCGCTCAGCTGACCTAGGGGCGGGGCCGGGGCGGGGACCTAAAGCCTCGGCTAC TTCCGAGGGGG

ATGAGGCTTCACCTGCTGCTCCTTC TCGCGTTGTGTGGCGCGGGTACAACCGCCGCGGAATTGAGTTATTCCTTGAGGGGGAATTGGTCCATC TGCAATGGCAACGGCAGCCTGGAACTTCCGGGCGCTGTACCGGGTTGTGTGCATTCTGCTCTTTTCCA ACAAGGGCTCATTCAAGATTCATACTACAGATTTAACGACCTTAACTATAGGTGGGTGAGCCTTGATA ACTGGACATATTCCAAGGAGTTCAAAATCCCTTTCGAAATATCAAAATGGCAAAAGGTTAATCTCATC CTTGAAGGCGTTGACACCGTTTCTAAAATACTGTTCAACGAGGTGACTATCGGAGAAACCGACAATAT GTTCAATCGATATTCTTTCGACATTACTAACGTGGTTCGAGACGTAAACAGCATTGAATTGAGGTTTC AGTCAGCAGTGCTCTATGCCGCCCAGCAAAGCAAAGCCCATACCCGGTATCAGGTACCTCCAGACTGC CCTCCTCTCGTCCAGAAAGGTGAATGCCATGTCAACTTCGTGAGGAAAGAGCAGTGCAGTTTCTCTTG GGACTGGGGTCCATCCTTTCCGACCCAGGGCATTTGGAAAGATGTTCGAATTGAGGCCTACAATATTT GCCATCTCAATTACTTTACCTTCTCCCCGATATACGACAAGTCCGCCCAGGAGTGGAATCTCGAGATA GAATCCACGTTTGACGTAGTTAGCTCTAAGCCTGTTGGCGGCCAAGTGATCGTAGCCATACCAAAGCT TCAAACACAACAGACGTACTCAATCGAGCTCCAACCAGGAAAGAGAATAGTGGAACTTTTCGTTAATA TTAGCAAAAATATAACCGTTGAGACCTGGTGGCCTCACGGCCATGGAAATCAAACGGGTTACAACATG ACTGTTTTGTTCGAGCTTGACGGGGGCCTGAATATAGAGAAAAGCGCCAAAGTTTACTTCCGGACCGT AGAACTTATCGAAGAACCGATTAAAGGTTCCCCGGGCCTGAGCTTTTATTTCAAAATAAACGGCTTTC CTATCTTTCTTAAAGGCTCCAATTGGATACCAGCAGATTCCTTTCAGGATCGAGTAACATCTGAATTG TTGCGACTGTTGCTGCAATCAGTAGTAGATGCCAATATGAATACGCTGAGAGTCTGGGGAGGCGGGAT TTACGAACAAGACGAGTTTTACGAACTCTGTGATGAGCTTGGGATTATGGTGTGGCAAGATTTCATGT TTGCATGCGCACTTTATCCCACTGACCAGGGTTTCTTGGACTCCGTCACTGCGGAGGTAGCATATCAA ATTAAAAGGTTGAAGAGTCACCCCTCAATTATAATATGGTCCGGAAACAATGAAAATGAAGAGGCTTT GATGATGAATTGGTATCACATTTCCTTTACCGATCGGCCAATTTATATAAAAGATTACGTGACGCTTT ACGTGAAGAACATACGGGAGCTTGTGTTGGCTGGAGACAAGTCCAGACCATTCATCACCAGTTCACCT ACGAATGGGGCGGAAACCGTAGCCGAGGCATGGGTATCACAAAATCCTAATTCCAATTACTTCGGCGA CGTGCATTTTTATGACTACATAAGTGATTGTTGGAACTGGAAGGTTTTCCCGAAGGCAAGGTTTGCGT CCGAATATGGCTATCAGAGTTGGCCAAGTTTTTCCACTCTCGAGAAAGTTAGTAGCACTGAAGACTGG AGCTTCAACTCCAAATTCAGTTTGCATCGGCAGCACCACGAAGGCGGAAATAAGCAAATGCTTTATCA GGCTGGACTCCACTTTAAACTGCCCCAGTCCACGGACCCGCTCCGAACGTTTAAAGACACTATATACC TGACGCAAGTCATGCAAGCACAATGTGTTAAGACGGAAACCGAATTTTACAGACGATCTAGGAGTGAG ATTGTGGATCAACAGGGCCACACGATGGGAGCTCTGTACTGGCAGCTTAATGACATTTGGCAGGCGCC CTCTTGGGCTAGTTTGGAGTATGGAGGTAAGTGGAAGATGCTTCATTATTTTGCTCAAAACTTCTTCG CGCCCCTCCTTCCCGTCGGTTTTGAAAACGAAAACACATTTTATATCTATGGGGTCAGCGATCTGCAC TCCGACTACTCAATGACGCTTAGCGTTCGAGTGCATACCTGGTCAAGTCTCGAGCCCGTCTGCTCTAG AGTCACGGAACGCTTTGTCATGAAGGGTGGGGAGGCCGTATGCTTGTACGAAGAACCTGTATCCGAGC TTTTGCGGAGGTGTGGTAATTGTACTCGAGAAAGCTGTGTAGTGAGCTTCTATCTTTCTGCTGACCAC GAGTTGCTTAGTCCTACCAATTATCATTTTCTGAGTAGCCCCAAGGAAGCGGTTGGCCTGTGCAAGGC GCAGATTACGGCGATTATTAGCCAACAAGGGGATATCTTTGTGTTCGACCTCGAGACCTCCGCCGTTG CCCCCTTCGTGTGGCTTGATGTGGGCAGTATCCCGGGAAGATTCTCCGACAACGGATTCCTGATGACA GAAAAAACTCGCACAATACTTTTTTATCCATGGGAACCGACTTCCAAGAACGAACTTGAGCAATCATT TCATGTGACGAGCTTGACGGATATATACGATTATAAGGACGATGACGATAAGTA

The LIPA protein sequence is:

(SEQ ID NO: 64) MKMRFLGLVVCLVLWTLHSEGSGGKLTAVDPETN MNVSEIISYWGFPSEEYLVETEDGYILCLNRIPH GRKNHSDKGPKPVVFLQHGLLADSSNWVTNLANS SLGFILADAGFDVWMGNSRGNTWSRKHKTLSVSQ DEFWAFSYDEMAKYDLPASINFILNKTGQEQVYY VGHSQGTTIGFIAFSQIPELAKRIKMFFALGPVA SVAFCTSPMAKLGRLPDHLIKDLFGDKEFLPQSA FLKWLGTHVCTHVILKELCGNLCFLLCGFNERNL NMSRVDVYTTHSPAGTSVQNMLHWSQAVKFQKFQ AFDWGSSAKNYFHYNQSYPPTYNVKDMLVPTAVW SGGHDWLADVYDVNILLTQITNLVFHESIPEWEH LDFIWGLDAPWRLYNKIINLMRKYQDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for LIPA and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

LIPA-DNA

(SEQ ID NO: 65) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG TGTATCTAAGAAGCAACTAACTTGCTTTTG ATTTTACCAGCTAATAGGTGGAAGGGACTTGCCTTGTCTCAGGTGAGACTTTGGACTATGGACTTTTG AGTTAATGCTGAAATGAGTTAAGACTTTGGGGGACTACTGGGAAGGCATGATTGGTTTTGAAATGTGA GGACATGAGATTTGGGAGTGGCCAAGGGCAGAATGATATGGTTTGGCTGTGTCCCCACCCAAATCTCA TCTTGAATTATAGCTCCTGTAATTCCCACATGTTGTGGGAGGGACCCGGTGGGAGATAACTGAATCAT GGGGGCAGTCTAGCCCATACTGTTCTTGTGGTGGTAAATAAGTCTCACAAGGTCTGATGGTTTTATAA GAGGAAAATCCTTTTACTTGGTTCTTTCTCTCACATGTGCCGCCATGTAAGACAAGCCTTTTGCCTTC TGCCATGATTGTGAGGCCTCCCCAGTCCTGTGAAACTGTGAGTCAGTTAAACCTTTTTCCTTCATAAA TTACCCAGTCTTGGGTATGTCTTTATTAGCAGCATGAGAACAGACTAATACACCTTCTAATTAGTCTC CCTGCTTCTGTAGTTCAGAATGATCTTTCTAAACTAGATTATGCTGCCCTTCTATTGAAAATATTACA CTGGCTTCTCATCTTACTCAGAAGACACGGTAAGATCTTGACAAGTGGCTCCCAAGGCACCAGACTTC TAGGACTTCATGTTCTATTACTTTCTACTATGTACATTCTGTTTTAGCCTCAAAGACCTCACCACTCT GGCTAGGACCCACCAGGAATATTCCTACCACAGGGCCTTTGTACCTGCTATTTTCACCCAGAATGTGC TTTCTCCAGTATCTAAGGCTGTTAACTACCTCCTTGCCTGTGCTCAGGTGTCACTTCATAAGAGTCCT TTCCTGATTACCATATACATATCATCCTCCTTATCCCTGTTTTTTTTTTTTTTTGGGGGATGGAGTCT CACTCTGTTGTCCATGCTGGAGTGCAGTGGCATGATCTCCGCTCACTGCAACCTCCACCTACCTGGTT CAAGCCATTTTCCTGCCTCAGCCTCCCAAGGAGCTGGGATTAGAGGCACACACCACCACACCCGCTAA TTTTGTATTTTTAGTAGAGATGGGGTTTCACCAAGTTGGCCAGGCTGGTCCTGAACTCCTGTCCTCAG GTGATCCGCCCTCCTCAGCTTCCCAAACTGCTGGGATTACAGGCGTGAGCCACTGTGCCCAGCCCCTT GTTGTTTGTTGTTGTTGTTGTTTGTTTGTTTTTGTTGTTATTTATAGCACTTATCACCACCTCATGTA TTATATAGTTATTCATGATGTGTCTCTTCCCATCAGAATATATACAAGAGAACAGGAACCTTGTTTGG TTGGTTTCTATACCTCCACTGTCTTACTAATGCCTGGCATTTAGTAGGTGCTCAATAAAATCTTTGTT TTAGAAAATGATTAATAAATAATATGTACATATTGAATATTGTTTCCTCTTTTAACAAATCTTTAATA ATAATAAAAAATTTAAAGCAGCAAGATTGCTTTGCATCAGGCACAATGATAAGCGCTTTAAATGGAGC CCATGATTCACTTTCATTTATAGAGCCCACATGCTCTCTGTCAGGCGCAGAAGGTGCCAGCCCTGCAG GAGCTTCGGGGGCGGAGCAGAAGGCCGCCTAAAACAGCCTTTGCTAAGAGAGCATGCGTAGGCGACGC GCTGGTAGAGCTGTGGACCTGCCAGCCTGCGAGGCGGAGGACGGGCTCCATCTCTTAGAAACGCCTAC GGCGCATGCTCTATGGGGTCAACTGGGGGGCTGGCAAGCGGCAGCGCTGGTCTGGGGCGGAGTCTCCG AGGCACTTCCCGGTGGCTGGCTGCTCTGATTGGCTGAACAAATAGTCCGAGGGTGGTGGGCATCCGCC CTCCCGACAAGGCAGACCAGGCCCCCTGCAGGTCCCCTATCCGCACCCCGGCCCCTGAGAGCTGG

ATGAAGATGCGCTTCCTTGGCCTCGTAGTTTGTCTGGTT CTGTGGACACTGCACAGTGAGGGTAGCGGCGGTAAATTGACGGCTGTAGATCCCGAAACTAATATGAA TGTTAGTGAAATAATCTCTTACTGGGGATTTCCATCCGAGGAGTATCTTGTAGAAACAGAAGATGGCT ATATACTTTGTCTCAACCGGATACCACACGGACGGAAAAACCACAGCGATAAGGGGCCAAAGCCGGTG GTTTTCCTTCAACACGGTCTTCTGGCAGATTCTAGTAATTGGGTTACCAACCTTGCAAACTCTTCACT TGGATTCATTCTTGCGGATGCTGGATTTGACGTATGGATGGGGAACTCCAGAGGGAATACGTGGTCCA GAAAACACAAGACATTGTCTGTATCTCAAGATGAGTTCTGGGCATTCAGTTACGACGAAATGGCGAAG TATGATCTCCCAGCATCCATAAATTTCATCCTGAACAAGACTGGTCAAGAACAAGTATATTACGTCGG ACACAGTCAAGGCACTACTATTGGCTTTATCGCTTTCTCCCAAATCCCGGAATTGGCGAAAAGAATCA AGATGTTCTTCGCATTGGGTCCGGTGGCGTCTGTCGCTTTTTGCACCAGCCCCATGGCGAAACTTGGG AGGTTGCCGGATCATCTCATAAAGGACCTCTTTGGAGATAAAGAGTTTCTTCCTCAAAGCGCATTTCT TAAGTGGTTGGGAACACATGTCTGCACTCACGTGATCTTGAAAGAACTTTGTGGAAACCTGTGTTTCC TCCTGTGCGGGTTCAATGAACGAAATCTTAATATGTCCAGGGTGGACGTCTATACCACCCACAGCCCG GCAGGTACGTCAGTCCAGAATATGTTGCATTGGAGCCAAGCGGTAAAGTTCCAAAAATTCCAGGCATT TGACTGGGGTTCTTCAGCTAAGAATTACTTCCACTATAATCAGAGCTACCCGCCCACTTATAATGTCA AGGATATGTTGGTTCCAACTGCAGTTTGGAGCGGCGGGCACGATTGGCTGGCGGATGTGTATGATGTG AATATCCTTCTCACACAAATTACTAATCTCGTGTTCCACGAGAGCATACCAGAGTGGGAACATTTGGA TTTTATATGGGGACTGGATGCTCCATGGCGGCTCTACAATAAAATCATCAATCTGATGCGGAAATACC AAGACTACAAAGACGACGATGATAAGTA

The CTNS protein sequence is:

(SEQ ID NO: 66) MIRNWLTIFILFPLKLVEKCESSVSLTVPPVVKL ENGSSTNVSLTLRPPLNATLVITFEITFRSKNIT ILELPDEVVVPPGVTNSSFQVTSQNVGQLTVYLH GNHSNQTGPRIRFLVIRSSAISIINQVIGWIYFV AWSISFYPQVIMNWRRKSVIGLSFDFVALNLTGF VAYSVFNIGLLWVPYIKEQFLLKYPNGVNPVNSN DVFFSLHAVVLTLIIIVQCCLYERGGQRVSWPAI GFLVLAWLFAFVTMIVAAVGVTTWLQFLFCFSYI KLAVTLVKYFPQAYMNFYYKSTEGWSIGNVLLDF TGGSFSLLQMFLQSYNNDQWTLIFGDPTKFGLGV FSIVFDVVFFIQHFCLYRKRPGLQAARTGSGSRL RQDWAPSLQPKALPQTTSVSASSLKGDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for CTNS and the 5′ and 3′ UTR sequences are listed below using the same

CTNS-DNA

(SEQ ID NO: 67) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGAGGAACTTGGTTAGGTACCTTCTGAGGCGGAAAG AACCAGCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAG TATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGA CGTCAATGACGGTAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATG AAACTGAGGCACGAAAATCACTTGAACCCG GGAGGCAGAGGTTTCAGTGAGCAGAGATTGCACCACTGCACTCCAGCCTGGGTGACAGAGCGAGACCC TGTCTCAAAAAAAAAAAAAAAAAAAAAAGAAGTGCTCTATTTCAGGAGAAACTGGCACTTTCTGAGCC TACTCTCCCCTAATGCCAGCTCTCCTGCTCACCCCACCAGGGTCAGAGCCAACTTTGCCTCCAATTCA TAGTCCTTTAAGTAAGAATCCTTTTAATATGCCCTAATGTCCCAACCAAACTAATCTTGAAAGCTTCT ATGTAGATACAAAGTGCTCCTGAAATCCCTATCCTCAGAAATGCTTCTGAGCCAAATGGGCTCTGAAC CCTAAACAACCGTGTCCATGTATGTGGCAAGAGCTTGTGAAAAACAAAGCTGGGCCAGGCGCAGTGAC TCACAACTGTAATCCTAGCACTTTGGGAGGCTGAAGTGGGCAGATCACTTGAGGTCAGGAGTTCAAGA CCAGTCTGGCGAACATGGCGAAACCCTGTCTCTACTAAAAATACAAAAAGTAGCCGGGCGCGGTGGCT CACACCTGTAGTCCCAGCTACTCGGGAGGCTGAAGCAGGAGAATCACTTGAATCCAGTTGGCGGAGGT TGCAGTGAGCCCAGATCACGCCACTGTACTCCAGCCTGGGCAACAGAGCGAGACTTGGTAAGAAAGAG AAAGAAAGGAAAGAATGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAGGAAG GGAAGGAAGGGAAGGAGTCTCGCTCTGTCACCCAGGCTGGAGTGCAACGGAGCGATCTCGACTCACTG CAAGCTCCGCCTCCCGGGTTCGCGCCATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGACTACAGGCG CCCGCCACCACGCCCCGCTAATTTTTTGTATTTTTAGTACAGACGGGGTTTCACCGTGTTAGCCAGGA TGGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGCGCTGGGATTACAGGCGTG AGCCACCGCGCCCGGCTGACCAAAGGTTTCTTGGTCCGCATTCTGCTTCTGTGGAATGAGCCAGGAGC CAGTTAGGCCTGATTTGACATCTGATTTCCGGAGGAAAACCCAGACTCTGCCCTGGGCAACAAACTGA ATCCTGAACTTGAGGTCACAGGGCAGGTGTGAGGAGCGGAGAGCAGCAAGAGTGAAAGGGAGGCCTGT GGTCATTCCATACACACAAGAGATCAGTTCCTCCAAGGTCAGGGGACAGAGAGCACAGGGATCCAGCG CCAAGCGCAAGGCCCCCAGAAGAAGCCAGAGAGTCGGGGAGGGGGCGGGGGGGAATCGGTCCCAGCAG GTGGGAAGGATTCTGGGACCAGACCTAAGGGATCATGAGCACAGCTGCTGCAGGCAGACGGGCCCCTG GAGAAGCTGGGGACAAGCTGGAATAGAGACTTCATTGCGGGAAGGGCTGTCAGGGAGGCCTCCTGGGG TGGAAAAGGGTGGTCAGGAGGCTCCTGGAGGCGGCGCGGCCCCGGGGGTCCAACTCACCTGGGGCCCG GCCACCGCGCTCTCGACCGCCGCCTCTGCCCGCGCAGCACGGGCACAGCTCGCCAGCACTGCGAACCC GGATGGGTCGTCGGGCGCGGCCCTCAGCAGAGCTGCCTTCACAGATGTGGTGCCCAGGTCAATGCCGA GGGTGATCGGCCGCGCAGCCATTATCTCCCTGACCCGCGCAGCTCCAGTCTGCAGCCAGCGGCCCCAC AAGTCCGCGCTCTTCGCCCAGGGGGGCGGGGCAGGGGCGGGGAGTCGCCTGCCAATCTTTCAGCCACA CCCAACATGGAGGCTTCTCGTCTTCCCACTGGCCGGGGAAGGCGAGCTTCCACGCAACCTCTCGGCGG GCCCCGGCTATAGGCGGAGAGGCGGCGGAAGGCGGGACCTAAAGGGGGCCCCGCCCCACGGGCTC

ATGATCCGAAACTGGCTGACCATATTCATCCTTTTTCCC CTCAAACTTGTCGAAAAATGCGAGTCTAGCGTCAGCCTCACAGTCCCTCCGGTCGTGAAACTCGAAAA TGGCTCCAGCACCAATGTGAGTCTGACGCTTAGGCCCCCCTTGAACGCTACCCTCGTTATTACGTTTG AGATTACTTTTAGGTCTAAAAATATCACTATACTGGAACTGCCTGATGAAGTGGTTGTGCCTCCTGGC GTCACCAATTCAAGTTTCCAGGTTACCTCACAAAACGTAGGGCAACTTACAGTCTACTTGCATGGAAA CCATAGCAATCAGACTGGGCCGCGCATCCGCTTCCTCGTTATTCGAAGTTCAGCGATATCAATTATCA ATCAAGTGATAGGATGGATATACTTTGTCGCCTGGAGTATTAGCTTTTATCCCCAGGTAATTATGAAT TGGAGAAGAAAATCTGTTATAGGGTTGTCATTTGACTTCGTGGCACTCAATCTTACGGGCTTTGTGGC ATATTCCGTATTTAACATAGGACTCCTTTGGGTGCCGTATATCAAAGAGCAATTTCTTCTCAAGTACC CCAATGGGGTAAATCCAGTGAACTCTAATGACGTCTTTTTCTCTTTGCATGCGGTCGTGCTTACACTG ATCATAATCGTACAGTGCTGCCTTTATGAGCGGGGAGGCCAGAGGGTATCATGGCCTGCAATCGGTTT TTTGGTCCTTGCCTGGCTTTTCGCTTTCGTTACTATGATCGTTGCGGCAGTGGGCGTAACAACATGGC TTCAATTTCTCTTTTGTTTTTCTTATATAAAGCTGGCAGTCACTCTGGTCAAGTATTTTCCCCAAGCA TACATGAACTTTTATTACAAGTCTACTGAGGGGTGGTCCATTGGGAACGTCCTCCTTGATTTTACAGG TGGCTCCTTCAGTTTGTTGCAAATGTTTCTCCAAAGCTATAATAATGACCAGTGGACATTGATATTTG GCGACCCGACTAAATTCGGGCTCGGTGTATTCTCTATCGTTTTCGACGTTGTATTCTTTATACAGCAC TTCTGTCTCTATAGAAAACGCCCTGGTCTTCAGGCTGCCAGAACCGGTAGCGGTTCTCGGCTGAGACA AGATTGGGCGCCATCTTTGCAACCCAAGGCGTTGCCACAAACAACTTCTGTAAGCGCATCCTCTTTGA AGGGAGACTATAAAGATGATGACGATAAGTA

The GNS protein sequence is:

(SEQ ID NO: 68) MRLLPLAPGRLRRGSPRHLPSCSPALLLLVLGGC LGVFGVAAGTRRPNVVLLLTDDQDEVLGGMTPLK KTKALIGEMGMTFSSAYVPSALCCPSRASILTGK YPHNHHVVNNTLEGNCSSKSWQKIQEPNTFPAIL RSMCGYQTFFAGKYLNEYGAPDAGGLEHVPLGWS YWYALEKNSKYYNYTLSINGKARKHGENYSVDYL TDVLANVSLDFLDYKSNFEPFFMMIATPAPHSPW TAAPQYQKAFQNVFAPRNKNFNIHGTNKHWLIRQ AKTPMTNSSIQFLDNAFRKRWQTLLSVDDLVEKL VKRLEFTGELNNTYIFYTSDNGYHTGQFSLPIDK RQLYEFDIKVPLLVRGPGIKPNQTSKMLVANIDL GPTILDIAGYDLNKTQMDGMSLLPILRGASNLTW RSDVLVEYQGEGRNVTDPTCPSLSPGVSQCFPDC VCEDAYNNTYACVRTMSALWNLQYCEFDDQEVFV EVYNLTADPDQITNIAKTIDPELLGKMNYRLMML QSCSGPTCRTPGVFDPGYRFDPRLMFSNRGSVRT RRFSKHLLDYKDDDDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GNS and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

GNS-DNA

(SEQ ID NO: 69) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC AATAATGACGTATGTTCCCATAGTAACGCCAATAG GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA TCATATGCCAAGTACGCCCCCTATTGACGTCAATG ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT CTACGTATTAGTCATCGCTATTACCATG TCTTGCCTAGGCTAGATTGCAGTGGTGCAGTCATA GCTCACTGCAGCCTCGAACTTCTGGGCACAAACAA TCCTCCCACCTCAGCCTCTTAAGTAGCTGGGACTA CGGGCATGCACTACCATGCCCAGCTAATTTTTATA TTTTTTGTAGAGCCAGGGTCTTGCTGTGTTGCCCA GACTGGTCTCAAACTCCTGGCCTCAAGCAGTCCTC CTGCCTCTGCCTTCTAAAGTGCTGGGATAACAGGT GTGAGCCACTGCACCGGGCCTAAAGTCTAAATTCC TATGTGGCCCTGCATCACTGACTCCTGCCTGCCTC TCTGACCTCATCTTACCTCACTCTCCCTTTTCCTC CCTAAGCTGCTTCCATCACCACACTGGCTTCTCTG TTTCCTCCCAGGTGCCTCTCTCCTTCCTCTGGCAG CCCTTGTACTTGCTATATACCCAGCCTGAAACATC TTCTGAATTTTTGCATGACTGACTCCTCATCGCAT GGCTCTCCGTACTGAAGTTACCTCCTGAGAGGCCT TTTCTGACCACCCATCTAAAGTAGTTCCCCTTTCT TCCCACCAGCTGTAATCACATCATCCTGGTTTATT CTCTTCATAGCACTTACCACCACCTGAAATGACTG ATTGTTTACCTGTTAGTTGTTTTAAGTCCCCAAGA GTGCAGAGATCATGAGGGCGAGGACCATCTATCCT CTGTCCACCACTGCCTAGATTAATGCCTGGCACGT GTTGTGTTTAATAAATGTTATTACACAGTCTTACT GTAAATCAGATATTCTTTCATAATTTTACATATTT ATCAGACAGTTTGACAATTAAGTCCCATACAGTCA ACTCTGGTCCTTTTCTCCACTTACTCTTTGAATCC TCATTTCACCTTCAAATGTCCTCACAGTAACTCAG GTGTTTTATCAAACCAATGTCTCATGAAGCCCAGT ATTCTTTTCCTGAGGATGGTACCCAGTGATGCTTT GAGGAGAGTATGGCTGACGACCTTGCTTCGGAAGG CTGGCGAAGATCTTCTGCTTCTCTAGCGTCTCTTG GCAGCCTCTTCTGGATCTACTCATGAAATTATCAG AGCTTTTTTTGGATAAGTTAGAATCCTCATCCTTT TGAGTTTATGGATTCCGTAGGTTTTGTATTTATAT AAAACAATGGGGAAAAGTCATTTATACATTATTGA AAATGAGGCTCCTGTTAACCTACTTATGTATTTAG ATTAGCAATCTTTAAGGAATTATTGCACAACAAAA TATACTTAAAACTGCATTCAATATGGTCTTAGGTT TCAAAGGTATCTCAGAATCATCGTGAACTGACCCA TATTACAACTAAAATGACCTCTTCAATGGTGCTTT TTGCTGTCTGGAATCTGAAGAATATTAGTGTTCCT TTTATTCGTATTTAAATGACTGTCTTCATACTTTT GTCCTCATTCTAGAAGGAAGTTAATTGTTCTCTGT ACTTGTAAGGATCTTAGATTTTGAACAAAAGATGA AAAGCAGGACATAAAATAGTTTCTGAGTAGCCTTT TGCCTGACAGTGTTCTGTGTACACCTGCTTGCCAC CTGGTTCAAGTCCTTATCCTGAGGTGCTTGTGGGT CTATGCAGACAACAGTAGTTGGTAGTTGAACAGTG TGTGTCTGGCCTCCACCACTGAGTGTGTGAGGTTT GAATCAGTCTCGGAGTCCTGGGGCCTTGTCTGGCT TTCAGAATCCAACTGTTGTCTTACTTCTGTTCTAT AGGGCGGAAGGCTCCCTTTATATCATTTCCCACAT CCTACTTCTAAAGATTAATTCATGGAGATAGGTCT GCCCTATCTGCCTTATCTGGGCGCTGATGACTAAT AAGGGCACAAAGATGTTATTGCCATCAACTGAACT TTCCCTTCCTGCAAGCATTTTGACTTCCTGCACTT TTATACAGGATGGAGCTGGCCGGAACCAAACTTGT CTCTAGAATCATACAAGACTCTCTTTGGCTGTTGC TTAGAGCTGACCATTTGGGAATAAAAGATTGAGTA AGATGTAACAAAACAGGAATTCTGGGCTGTGTGTC TCAATTTATTGGAAGAAATTGTTTAATGGATAATT ACTTACTTTTAC

ATGAGGCTCCTGCCGCTCGCCCCGGGACGGCTCAG AAGAGGGTCTCCAAGGCACCTCCCAAGTTGTTCCC CCGCGCTTCTCTTGCTTGTGCTGGGAGGATGTCTC GGAGTTTTTGGCGTTGCGGCGGGAACACGACGGCC AAACGTTGTCCTCCTCTTGACGGATGATCAAGACG AGGTGCTGGGGGGTATGACACCGTTGAAGAAGACC AAAGCACTGATAGGTGAGATGGGTATGACTTTCAG CAGCGCTTATGTTCCGTCTGCCCTTTGCTGCCCTA GCCGCGCCAGTATCCTTACGGGGAAGTACCCACAT AATCACCATGTAGTTAACAACACCTTGGAAGGTAA TTGCTCTTCAAAGTCCTGGCAGAAAATTCAGGAAC CCAATACCTTCCCGGCCATACTTCGATCTATGTGT GGATATCAAACATTTTTCGCCGGGAAGTATCTCAA TGAATACGGTGCTCCCGATGCGGGCGGACTCGAAC ACGTTCCCCTGGGTTGGAGCTATTGGTACGCACTC GAGAAAAATTCAAAGTACTATAATTACACCTTGTC TATAAACGGAAAAGCCCGGAAACATGGTGAGAACT ATTCTGTCGACTATCTGACGGACGTGCTGGCGAAT GTAAGCCTCGATTTTCTTGATTACAAGAGCAATTT CGAACCTTTCTTTATGATGATCGCAACGCCTGCTC CCCATAGTCCATGGACTGCGGCACCACAATATCAA AAAGCGTTTCAGAATGTCTTTGCCCCACGAAACAA AAACTTTAATATACACGGCACCAATAAGCATTGGC TGATAAGACAAGCGAAGACACCCATGACCAATTCA AGCATACAGTTCCTGGACAACGCATTCCGCAAGAG GTGGCAAACGCTGCTCTCAGTTGACGATTTGGTTG AGAAATTGGTAAAAAGACTTGAATTTACTGGCGAA CTGAACAATACGTATATCTTCTATACATCTGATAA CGGATACCACACTGGTCAGTTTAGTCTCCCCATAG ATAAACGGCAGCTCTACGAGTTCGATATCAAAGTA CCCTTGTTGGTAAGGGGACCGGGAATAAAACCTAA CCAGACGTCCAAAATGCTGGTGGCAAACATCGACC TCGGCCCAACGATTCTGGACATCGCTGGGTATGAC CTTAACAAGACACAAATGGATGGCATGTCCCTGCT GCCAATCCTCAGAGGGGCCAGCAATCTTACATGGC GCTCAGATGTCCTGGTAGAATATCAAGGTGAGGGA CGGAATGTAACAGACCCTACCTGTCCCAGCTTGAG CCCTGGTGTATCTCAGTGTTTTCCTGATTGTGTTT GTGAAGACGCATACAATAACACATACGCTTGTGTA AGGACGATGAGTGCACTTTGGAACTTGCAGTATTG CGAGTTTGACGATCAGGAGGTGTTTGTTGAGGTGT ATAACTTGACGGCAGATCCGGACCAAATTACCAAT ATAGCTAAAACCATTGATCCGGAACTCCTCGGCAA GATGAATTATAGACTTATGATGCTGCAGTCATGCA GTGGTCCCACATGCCGAACGCCAGGAGTGTTCGAC CCTGGGTACCGGTTCGATCCCCGCCTGATGTTCTC CAATAGGGGTTCAGTTCGGACGAGGAGATTCTCAA AGCACCTCCTTGACTATAAAGATGACGACGACAAG TA

The HGSNAT protein sequence is:

(SEQ ID NO: 70) MSGAGRALAALLLAASVLSAALLAPGGSSGRDAQAAPPRDLDKKRHAELK MDQALLLIHNELLWTNLTVYWKSECCYHCLFQVLVNVPQSPKAGKPSAAA ASVSTQHGSILQLNDTLEEKEVCRLEYRFGEFGNYSLLVKNIHNGVSEIA CDLAVNEDPVDSNLPVSIAFLIGLAVIIVISFLRLLLSLDDFNNWISKAI SSRETDRLINSELGSPSRTDPLDGDVQPATWRLSALPPRLRSVDTFRGIA LILMVFVNYGGGKYWYFKHASWNGLTVADLVFPWFVFIMGSSIFLSMTSI LQRGCSKFRLLGKIAWRSFLLICIGIIIVNPNYCLGPLSWDKVRIPGVLQ RLGVTYFVVAVLELLFAKPVPEHCASERSCLSLRDITSSWPQWLLILVLE GLWLGLTFLLPVPGCPTGYLGPGGIGDFGKYPNCTGGAAGYIDRLLLGDD HLYQHPSSAVLYHTEVAYDPEGILGTINSIVMAFLGVQAGKILLYYKART KDILIRFTAWCCILGLISVALTKVSENEGFIPVNKNLWSLSYVTTLSSFA FFILLVLYPVVDVKGLWTGTPFFYPGMNSILVYVGHEVFENYFPFQWKLK DNQSHKEHLTQNIVATALWVLIAYILYRKKIFWKIDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for HGSNAT and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

HGSNAT-DNA

(SEQ ID NO: 71) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC AATAATGACGTATGTTCCCATAGTAACGCCAATAG GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA TCATATGCCAAGTACGCCCCCTATTGACGTCAATG ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT CTACGTATTAGTCATCGCTATTACCATG CAAAAGGGTAAAGTTGTTTACCATTCGGACTTTTG GCCCCCTTCTCCGTGTACAAATTGGTAAAAAGCCT CAGGATTTTTGAGCTGTCCTTATCCCTCCCCTTGT TTCTTTTCTTTTCTTTTTTTTTTTGAGACAGGGTC TCACTCTGTCGCCCAGGCTGGAGTGCAGTGATGTG GTCTTGGCTCACTGCAACCTCCGTTCAAACGATTC TCCTGCCTCAACCTCCTAAGTAGCTGGGAGTACAG GCAGGCACCACCACTGCTGGCTAATTTTTGTATTT TTAGTAGAGACAGGGTTTCACCATGTTGGCCAGGC TGGTCTTGAACTCCTGACCTGCCAGGCTGGAGTGC AGTGGCATAATCTTGGCTCACTGCAAACTCTGCCT CCCGGATTCAAGTGATTCTCCTGCCTCAGCCTCCC AAGTAGCTGGGACTACAGGTACTTGCCATGACGCC CGGCTAATTTTTTGTATTTTTAGTAGTGACAGGGT TTCACCATGTTGGCCAGGATGGTCTCGATTTCTTG ACCTCGTGATCCACCTGCCTTGGCCTCCCAAAGTG CTGGGATTACAGGCGTGAGCCACTGTGCCCGGCCA TATGTGTTTAATAACCCAGTTTGTCTCTTCTTGCC TTCAGGACATCAAACGGTCATGCTACTGGAAGCTC GGACCATGGCCCCTTCTGCTGGGCACCCTTAGATA GGCCTCTGAGGGAGATCTGATTGCCATTTTCCCGA AACAGTGCCCCCTATCAGCAGGAAGCAGTTAAGAT CTGTCTTTGTCCCTATTCTTATCCTAGTGGCAGTT AGATAGACTTCTTTAGAGCGAGGAATGAGCCAGAT GGGAAGGGTTCCCTGGTAAAACTCCAACTGGCCTG TGCACTGCTCTGGGGTGGAGCCACAGAAGTTCGCT CCTCAGTTTGCAGCTGGGAGGAGCCTGGCCCTCCT CTTCCTCGGGAGAACCTGGGATTTAATCTGTGAGG TGGGAAGCCTACAACTAGGAGAACTCTGGCTCTGC TGAGTCCCTGTTCCCCTTTTTCTTCCTTTACACCC AATAAAACCCTGCCTTACCCTTCAAATTGTCTGCG AGCCTAATCTTTCCTGGCGTGTGACAAGGACCTCC ACCGTCTTTAGCTGAACTAAGGAAAAGTCCCGCAA CATTTTCATGTGTGCCTTTGTATTTTTATTACATA TATGGATGTCCCTAAACAACATACATTATTGTTTT GCTTTATATATTAAAAAGGCATTCTGCAATTTGCA TTTTCCCCAGCCTTGTGTTTTGAGATTTATCCATG TGGATGCGGGAAGCTGTAGAGCACTTCCCCTGCTG TGGGGCAGTTTGTTTTCTCGCTGGCGGACATTCAG CTTGTTGACAAGGTTTTGCAATTACAAGCACCTCT GCTATAGGTATTACTGTACCTGTCCCTTATACCTG CGATAGTGTCTCCCGGCATACAGCCAAGAATGGGT GTGCACACTCCTCGACCTGCTCCCTTCCACTTCGT CAGCCTGGCCGGGGGCTCTTTCAAGAGGTGGGGCC GCTTGGTGGCTTCTAAGTCGTGCCTCTCCCTCTGG GTAATAAACGCCTTGGGGGCAGGGACTTTGCAGTC TTGCTTATTGAGGCGTTTTCCAAAACAGGGACCGA GGGCTCTAACACCCGTGCGGAGGGTGGCCGGCGGG GGCGGGAGTTTGGCAGAATGCGGCTGGAGAAGGTG GGGCGAGGGAAGAAGGCTCCTGGCCTGCAGGGGCC TCTCTTCCGGCTGTTTTTCCTCCCGAAGACAAACA CTCCCAACGCAGGGGCGCAGAGCCTCGGCTTCTTT CCTGGCCAGCTCCCTCAAGGCAGGGCCTAGCATGG CCCGGCCCAGCCCCTAGGTTCCCCCGCCCGCGGCT CCCGGGCGCCTCCGCCTCCCGCGGTGACTCAGGCG GCGGTGACGGCAGCGGAGGGGGCGATGACGGGCGC GCGGGCGTCCGCGGCGGAGCAGCGCAGGGCGGGGC GCAG

ATGAGCGGCGCGGGCAGAGCTTTGGCGGCCCTTCT TCTGGCGGCATCTGTGCTTAGTGCAGCACTCTTGG CTCCTGGGGGAAGTAGTGGTCGAGACGCTCAGGCC GCGCCACCGAGAGATCTGGATAAGAAACGGCACGC AGAGCTCAAGATGGACCAGGCACTTCTGCTCATAC ACAACGAATTGCTTTGGACCAATTTGACGGTATAT TGGAAGAGTGAGTGTTGTTACCATTGTCTCTTCCA GGTTCTTGTGAACGTGCCACAGAGTCCTAAAGCTG GGAAGCCTAGTGCTGCGGCGGCATCTGTTTCTACA CAGCATGGTAGCATACTGCAACTTAACGACACTCT GGAGGAAAAAGAGGTATGTCGATTGGAATATAGAT TTGGCGAGTTTGGCAATTATTCATTGCTGGTTAAA AATATCCACAACGGTGTTAGCGAGATTGCATGCGA TCTCGCTGTTAATGAAGATCCGGTCGATTCTAACC TGCCGGTCTCAATAGCTTTTCTGATAGGGCTGGCA GTGATTATCGTAATCTCATTCTTGAGGTTGCTCCT CTCACTCGACGATTTTAACAACTGGATCAGCAAGG CAATTAGTTCCAGAGAAACTGACAGGCTCATTAAC AGCGAACTTGGTTCACCCAGTCGCACAGACCCCCT TGACGGCGATGTGCAACCTGCGACATGGAGATTGT CCGCCCTCCCTCCGCGACTGCGATCAGTGGATACC TTCAGAGGAATTGCGCTCATTCTTATGGTTTTCGT AAATTACGGAGGGGGTAAATACTGGTATTTTAAAC ATGCCAGTTGGAATGGACTCACCGTTGCAGATCTC GTGTTCCCGTGGTTCGTCTTCATTATGGGCTCATC CATTTTTCTCAGCATGACCTCCATCCTCCAGCGAG GATGCTCCAAATTTCGCCTCCTCGGAAAGATAGCC TGGCGAAGTTTCCTGTTGATTTGTATTGGGATTAT TATCGTAAACCCCAACTACTGTCTGGGGCCTTTGT CATGGGATAAAGTAAGGATACCTGGAGTTCTCCAA AGACTCGGCGTGACTTATTTCGTCGTTGCAGTTCT CGAACTCCTCTTTGCCAAGCCGGTCCCCGAGCACT GCGCATCAGAACGCTCATGCCTCAGCCTTCGCGAC ATAACAAGCAGTTGGCCTCAGTGGCTGCTTATCCT TGTCCTGGAAGGCCTTTGGCTTGGTCTTACCTTTT TGCTTCCCGTACCAGGATGCCCAACTGGCTACCTC GGGCCCGGAGGGATCGGCGACTTTGGAAAGTATCC CAATTGTACCGGAGGAGCCGCGGGCTATATTGATC GACTTCTCTTGGGGGATGACCATCTTTACCAACAC CCGTCTAGTGCAGTACTTTACCATACCGAGGTAGC CTATGACCCGGAGGGAATCCTTGGTACCATTAACT CAATAGTCATGGCGTTCCTTGGTGTACAGGCTGGA AAAATTCTCCTTTACTACAAAGCTCGAACGAAGGA TATTCTTATAAGATTTACAGCGTGGTGCTGCATCC TTGGACTGATTTCTGTGGCCCTGACGAAGGTATCC GAGAACGAGGGATTCATCCCCGTTAATAAGAATCT GTGGAGCCTTTCCTATGTCACCACGCTCAGCTCTT TTGCTTTCTTCATTTTGCTTGTTCTCTATCCAGTA GTGGATGTAAAGGGCCTGTGGACAGGGACTCCGTT CTTCTACCCGGGGATGAACAGCATACTTGTTTATG TGGGACATGAAGTATTTGAAAACTATTTCCCCTTT CAATGGAAACTTAAAGATAATCAAAGTCACAAAGA GCACTTGACACAAAACATTGTAGCGACAGCGTTGT GGGTCCTCATTGCATATATCCTCTACAGAAAGAAG ATATTTTGGAAGATAGACTATAAAGATGATGATGA TAAGTA

The NeuroD1 protein sequence is:

(SEQ ID NO: 72) MTKSYSESGLMGEPQPQGPPSWTDECLSSQDEEHEADKKEDDLETMNAEE DSLRNGGEEEDEDEDLEEEEEEEEEDDDQKPKRRGPKKKKMTKARLERFK LRRMKANARERNRMHGLNAALDNLRKVVPCYSKTQKLSKIETLRLAKNYI WALSEILRSGKSPDLVSFVQTLCKGLSQPTTNLVAGCLQLNPRTFLPEQN QDMPPHLPTASASFPVHPYSYQSPGLPSPPYGTMDSSHVFHVKPPPHAYS AALEPFFESPLTDCTSPSFDGPLSPPLSINGNFSFKHEPSAEFEKNYAFT MHYPAATLAGAQSHGSIFSGTAAPRCEIPIDNIMSFDSHSHHERVMSAQL NAIFHDDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for NeuroD1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

NeuroD1-DNA

(SEQ ID NO: 73) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC AATAATGACGTATGTTCCCATAGTAACGCCAATAG GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA TCATATGCCAAGTACGCCCCCTATTGACGTCAATG ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT CTACGTATTAGTCATCGCTATTACCATG TGTCGCGAACTGGAGGTTTCTGCTTTCTGGGGGTG AGGACAAGGATTTAGCAGAGGGACCTCTAGGCTAC CCCTGACCTCGAAGCTAGCTGGAGTCCTTTCTCCC ACTCCGTCCCCAGTTCTCCTCCGGAACTCCCCAAA GTTGGAAAAATGAGAGCCTAGGCACGAGTTGCATA TGCCTGCGGCATAGTGTGCTGCCAGTCGGGGCAGC TGCCGGGTGAGGGGCAGTACTTAACCTGGCCCTGC CGCAAACGTCGGGCTGTGTACTATCTTCTAAGGGC TAGTACTCCGACGCCCTCGAGTTTTAGCCCAACAC TGAAGATACAGACAGTACAGGGGTAAATCCTGGGC CCAGGCTCCTGGGTGAATTATTTTATCCTCCCCTA TGCGCTTTGTCAGCCAAGTGAATGTAGAAAAGCAA GCAAAACTCCAGAACCCCACAACGATTCACGCCAC GCTTCGGTGGCACAACTCTTTTCTTCCCCTTTTAG ATTAGTACTGTGCAGGGAAGGCTGCACCTGCTACC TTCAGACACCGGGGATCTGGCTAGGACCCTCTTCC TCTACCCCTACTCTCTCCTCCCGTCCCCACCCTCT CCCAGATGCACCCCAATCCAGCCTCTCAACCCTGT CGCTGTTTGCAAACTCGAGGGATGTTTAGTGCAAT TGCCTTTAAATAAGCAATTCACGTAAGAGGTATTT ATTGCAGAGGGTTTCAGGTCTGGGAGGGGGTAAGG AGTTAGTTAATGAAGGATTAGAGGCAAAGCTGGGA AAGAACGAGTAGACAGGCCAGTTTCTTTCTTTCTT TTTAAAATCTATTATTCTGGAAAACCCTTGTTCGA AAAGAGTAAAGAATTGCTATTTGGGCAACAATATG GCTCCTTCAGAACTGGTCGAGAATTTCTGTGGTCT TTGCTTGACCTTCAAGTTGGGAGTTTCAAATCAGA GGCTTTGAAGTCTGGAGGAGTTCGCAGCCATTAAT CCTTCCGGGGTTGTGCTAAAGGCGTTTCTAGAAAG AGATCGGAAAGACCCGTTCAGCACAGGCCCATTGC ATCTTCTCTTTGAAAACGCTTGTCTGAATCAAGTA TCTTATACAGACCCGAGACTGAGGGGAGCAAGAGC GCAGGTCCGGCTGTGGCGAGGTGTCCACCACCGTA CTTGTGGTCAATGCCTGGACTAGAGAGCCGAGGCC GTCCAGGGCGGGCTGGCCAGGGAACCAGAAGCGTC CCTGGACTGGCTGAGTGAGGGTGCCCTTTCCAGCA ACCCAGTGGCCATGGTTAAAAGGCAGAATACAACC GTCAAAGAAGTCCCCAGCTCCCACATAAGAGAGCG CAAAGGCCAATGGAACCAAGGCCTCCTCGCGAGAA CTAGCTCGCTTTGAGGACAAGATCCTGGGGATGGA GGTGGGGACTGACGTAGTGAGAGGGTCTGGAGGAA CAGTCGTAGCTGAAGGTCAGGACATGAAGAATTGC ACGTATGGTAGGGATAGAATGGCAGGTACAACTTT TCTGTACTGAAGGAACTGGGAGAGGACGATCCGGT TAGGGAGGTTGGGGAACTAATCTCAACGCTGCGTT TACAGATGAAGCCGCTTTTATATGGCGTATATGTT TGCTTAGAGGGGCCGACGGAGATTAGGAGAAGCCA TCCTTTGGCGCCAATGATCAAAGCGTCTGCCAAGG AGAAGAAGCCAAGGGATGGGCCTTTCAGAGAGGGC AAGGAGTCATGCTGCTCTGGATGCCAGTGTCAGGA CAAGAAATCGAAAGGAGCGAGGACTCTTCACTGCG TGCCTCAGTCTCCCCGCTTCTGCCTCTTTCACCTC TGTCCTACTTCCGGCGCGAAAGCAGGCCACTCGCT CTGATCTAGACCTAGTTAACATTAGCTTTTCCCTT CCTTCCCTCAAATCCCCTCCCCCCTCTATCCCCGT CCCTTCTGCCGCCTGAAAGGGTTAATCTCTCCTGC GGGTAAAAACAGGTCCGCGGAGTCTCTAACTGGCG ACAGATGGGCCACTTTCTTCTGGCCACAAAGGGGC CGGAATGGAGCGCTCCGCGGCATACAAATGGGCAG GTCACGTGGTTCCAGGCTCTTGGCTGGACCGGGAA GACCATATGGCGCATGCCGGGGAGGAAGGAGGAGG GGCGGGGGTAGGGGTGGAGGGTGAGGGGAGCGGTT GTCGGAGGAGGGCGGGAGACGAGCAAGGCGTGGGG AGAAGTGGGGAGGAGGGGAGAACGGGGAGCGCACA GCCTGGACGCGTGCGCAGGCGTCAGGCGCATAGAC CTGCTAGCCCCTCAGCTAGCGGCCCCGCCCGCGCT TAGCATCACTAACTGGGCTATATAACCTGAGCGCC CGCGCGGCCACGA

ATGACGAAAAGCTACAGCGAGTCAGGGTTGATGGG GGAGCCTCAACCCCAAGGGCCCCCATCTTGGACGG ATGAATGCCTGTCATCACAAGACGAGGAACACGAG GCAGACAAGAAGGAGGACGACCTGGAAACGATGAA CGCTGAGGAAGACAGCCTCAGGAACGGAGGCGAAG AAGAAGATGAAGACGAAGACCTGGAGGAAGAGGAG GAAGAAGAGGAAGAGGATGACGACCAGAAGCCCAA ACGGCGCGGGCCCAAAAAGAAGAAAATGACTAAAG CCAGGTTGGAGCGGTTCAAACTCAGGAGGATGAAG GCTAATGCAAGAGAGAGGAATCGCATGCATGGACT CAACGCCGCTCTCGATAACCTCCGGAAGGTCGTGC CATGTTATTCTAAAACACAAAAACTGTCCAAAATC GAGACCCTGAGGTTGGCAAAGAACTACATATGGGC GCTCAGCGAGATTCTTAGATCTGGTAAGTCTCCGG ACCTCGTTTCCTTCGTCCAAACCCTGTGTAAAGGT CTGTCACAGCCAACCACCAACCTTGTAGCTGGGTG CTTGCAGTTGAACCCCCGCACTTTCCTTCCTGAAC AAAATCAGGATATGCCTCCGCACCTCCCTACCGCC AGTGCATCTTTTCCGGTACATCCCTACTCATACCA AAGCCCGGGTCTGCCTAGTCCGCCGTATGGTACAA TGGATTCCTCCCACGTGTTCCACGTAAAACCCCCA CCTCATGCCTATTCCGCTGCCTTGGAGCCTTTTTT TGAGTCTCCGTTGACAGACTGCACCAGTCCTTCTT TTGATGGGCCCCTGTCACCTCCTCTTAGCATCAAT GGAAACTTCTCTTTCAAACACGAGCCAAGTGCAGA GTTCGAGAAAAATTATGCTTTTACTATGCACTACC CCGCAGCTACCCTGGCAGGTGCGCAAAGTCATGGA TCTATCTTTTCAGGAACGGCTGCGCCGAGGTGTGA GATACCCATTGATAATATCATGAGTTTCGATAGCC ACAGCCATCACGAGCGCGTGATGAGCGCTCAACTG AATGCAATTTTTCATGACGACTATAAAGATGACGA CGATAAGTA

The SLC17A5 protein sequence is:

(SEQ ID NO: 74) MRSPVRDLARNDGEESTDRTPLLPGAPRAEAAPVCCSARYNLAILAFFGF FIVYALRVNLSVALVDMVDSNTTLEDNRTSKACPEHSAPIKVHHNQTGKK YQWDAETQGWILGSFFYGYIITQIPGGYVASKIGGKMLLGFGILGTAVLT LFTPIAADLGVGPLIVLRALEGLGEGVTFPAMHAMWSSWAPPLERSKLLS ISYAGAQLGTVISLPLSGIICYYMNWTYVFYFFGTIGIFWFLLWIWLVSD TPQKHKRISHYEKEYILSSLRNQLSSQKSVPWVPILKSLPLWAIVVAHFS YNWTFYTLLTLLPTYMKEILRFNVQENGFLSSLPYLGSWLCMILSGQAAD NLRAKWNFSTLCVRRIFSLIGMIGPAVFLVAAGFIGCDYSLAVAFLTIST TLGGFCSSGFSINHLDIAPSYAGILLGITNTFATIPGMVGPVIAKSLTPD NTVGEWQTVFYIAAAINVFGAIFFTLFAKGEVQNWALNDHHGHRHDYKDD  DDK

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for SLC17A5 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

SLC17A5-DNA

(SEQ ID NO: 75) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC AATAATGACGTATGTTCCCATAGTAACGCCAATAG GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA TCATATGCCAAGTACGCCCCCTATTGACGTCAATG ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT CTACGTATTAGTCATCGCTATTACCATG GTCAAACTAAGCAAAGGGTATGGAGAACTCACTGT ACTATCTTTGCAACGTTTATGTAAACCTAAAATTT CTAAAATAAAAAATATTAAAAAAAAGAATTCCTCT GGTTTGAAGTCTTTCAAGTCTGTTGCAACTATATT CCCTGGCCCAAGTTATCTATAACCTTGGTCATCTG GGAGCTTGTTAGCAATACAGAATCTCAGGCACATC CCAGATGTACTGGGCTTCTCAGAGAAACAGCCCCA ATTGGGTAGTTTGGGTAATAAAGTTTTGGCTTTCA CAATATAGGCTGGCCAACTCGACCCAAAACAGATG ATGGTGCACATGCCTGGAGACCCAGGAGGACCTGT GGTGCAGATGAAGTCTGAGGACACTCTGCTGGAGA AGTCTCCCTTGCTTGGGCAAGAGAAGTGGGGGAGT CGGATTTTTTATTCTAGATAGGCCTTCAACTGATT GAAGGAAGCCCACCCAGATTATGGAAGGCAGCCAT CTTTACCCAGAGTTCAATGATTTTAGTGTTAACCT CATCCAAAGACAACCAGCAAGTTAACACATAAAAT TAACCATCACACCAGATCTGCTGAATCTGAATCTA CATTTTAAAAGGATTTGCCAGGTGACTCTGCATAA TCCAGTTTGAAAATTGCATTTTTCTACAACCCTTA GAGAGTGTAAAAATCTACATGGTAATTCAGTAACT CAGAAACAAGGCTTGATTTGCTGCTTTAACTTGAG AACTTTTCTAGCATTTACTGATCTGGAGGTAGGGA TGCCTACAGAAATCCTCGCCCTCCCTTCTAGGTAA AGGACCCTCCCCTTTGTTCTCACGTGAACCTCACT AAGCTTCTAACCTGGTTTACTGAATTAGTGGCTTG TGGGTCTTCCCTGTCTACACCAAACTCTCCGAGAG CATCTACATCTTATTTTCTACCTCCACAGAGACAG CCTTTATTGGCGGATCCAGATCTGCCCTGCCAAGG CAAGCTGGGTTTTCCTAGTTTCACTTTCAGAGTCC GCAAATGCTAGCACAATCTATCCAAATTCTATCGT GGAGATAAAGCATGCACACATACATCAGAGGATTC CATAGGTCGAACCATATGAAACTACCTATGTTGAT TACTTTTACCTATAAAACCAGCAACATCATAGGAC TCAACAAATTTCCATTGCTGTTTTTCCGCCTAAAA GCTATTTTAGGACCAGGAGCAGTGGCTCACGCCTG TAATCCCAGCACTTTGGGAGGCCGAGGAGGATTGC TTGAGCCCAGGAGTTCGAAACCAGCTTGGGCAATA TAATAAGACCAAGCCTCTACAAAAATAAAAAGTAG AAACAAAATTAGCCAGATGTGGTGGCATGCTCCTG TAGTCCCAGCTACTTGGGGGAGCTGAAGAGAATCG CTTGAGTCCAGGAGTTGGAGGTTGCAGTGAGCTGC GATTGCGCCACTGCATTCCAGCTTGGGCAACAGAG CAAGACCCTGCCTGGGAGAAAAAAAAAAAAAAAAA AAAGCTATTTTAGGGACAATATGCCGCCACAGTCA CGAGGTAAATATGCCGCCACAGTCACGAGGTAGAT CGTACAAAGGTTGCTAACAGTATGGCAACTGACCG CTAACAAGCGAATGTCAAGTTGTGAAATGCACACC ACCCACTTCCCTAGTTCGGTCGAAGCCCTCCCCTT AATTATGTGCAATTCAAGTCCCCACTGCCCGCCCG CAAGCCCCCACTCATCCTCGCTGCGGGCAGGGTGG CCCCTGCACTTTACAAGGGGGTGCAGGAGCGGGAG ACGGTCGTCCGAACACCGGCTCCCCGGCATGCGTA GACCGGCGGGCGGAGCGGGCTCACTTTGCGCCAAT CCTACGAGAACTCCCAGAACTCCGCTTCCCTAGTC CAACCCAAGCCAGAGTTGCCCACACCTAAGATGGC GGCGGGGGCGGAGTCGGCGCGGCCGCCTCTGGGCG GGACCGCGGGGACTAGACGTGGCCGCGGGGCGGTGT CAT

ATGCGGAGCCCCGTGAGAGACCTGGCCAGAAACGA TGGGGAAGAGTCTACAGACCGGACCCCGTTGCTTC CGGGTGCTCCCAGGGCAGAGGCCGCCCCTGTCTGT TGTAGCGCACGCTACAACCTCGCCATACTTGCTTT TTTCGGGTTCTTCATAGTTTACGCCCTGCGGGTGA ACCTTAGCGTAGCTCTTGTAGATATGGTCGACTCT AACACTACTCTGGAAGACAACAGAACCTCTAAAGC GTGTCCAGAGCACTCAGCCCCTATTAAGGTACACC ATAACCAAACCGGAAAAAAGTATCAGTGGGACGCG GAAACCCAGGGGTGGATACTCGGCTCATTTTTCTA CGGTTATATTATCACCCAGATTCCTGGAGGCTATG TAGCCTCCAAGATCGGTGGGAAAATGCTCTTGGGA TTCGGCATTTTGGGTACTGCGGTACTTACCCTGTT CACTCCTATAGCAGCCGATCTTGGGGTTGGCCCAT TGATCGTTCTCAGAGCCCTCGAAGGTCTGGGAGAG GGCGTTACATTTCCAGCAATGCACGCGATGTGGTC AAGTTGGGCGCCACCCTTGGAGCGAAGCAAACTTC TCTCCATTTCATATGCAGGGGCCCAGCTGGGAACT GTAATAAGTCTGCCGCTGAGCGGTATAATCTGCTA CTATATGAATTGGACATACGTCTTTTATTTTTTCG GAACAATAGGGATTTTCTGGTTTCTCTTGTGGATA TGGCTGGTTAGCGATACCCCGCAGAAGCACAAACG CATAAGTCACTATGAAAAAGAGTACATCTTGTCTT CACTTCGCAATCAACTGTCTTCTCAAAAGAGCGTG CCTTGGGTACCGATATTGAAGAGCCTGCCTCTCTG GGCAATCGTAGTAGCGCACTTTTCATATAATTGGA CCTTTTACACACTGTTGACTCTTCTCCCAACGTAT ATGAAGGAAATTCTCCGATTTAACGTGCAAGAAAA TGGATTCTTGTCATCACTTCCTTACTTGGGTTCAT GGCTCTGCATGATTTTGTCTGGTCAGGCGGCCGAT AATCTGCGCGCCAAATGGAACTTTTCTACCTTGTG TGTAAGACGAATCTTTTCCTTGATCGGCATGATAG GCCCCGCTGTGTTTTTGGTAGCAGCCGGCTTCATT GGGTGCGATTACTCACTGGCTGTCGCGTTTCTCAC AATTTCTACCACACTTGGCGGTTTTTGTAGCTCTG GCTTCAGCATAAACCATCTCGACATAGCACCTTCC TACGCGGGTATACTGTTGGGTATCACAAATACCTT TGCCACAATCCCAGGTATGGTCGGCCCAGTTATAG CCAAATCTCTGACTCCTGACAATACTGTAGGAGAA TGGCAAACAGTATTCTATATCGCCGCTGCTATCAA TGTTTTCGGGGCAATTTTCTTCACGTTGTTCGCGA AGGGGGAAGTCCAAAACTGGGCTCTTAATGACCAT CATGGGCACAGGCACGACTACAAGGATGATGATGA  TAAGTA

The CLN6 protein sequence is:

(SEQ ID NO: 76) MEATRRRQHLGATGGPGAQLGASFLQARHGSVSADEAARTAPFHLDLWF YFTLQNWVLDFGRPIAMLVFPLEWFPLNKPSVGDYFHMAYNVITPFLLL KLIERSPRTLPRSITYVSIIIFIMGASIHLVGDSVNHRLLFSGYQHHLS VRENPIIKNLKPETLIDSFELLYYYDEYLGHCMWYIPFFLILFMYFSGC FTASKAESLIPGPALLLVAPSGLYYWYLVTEGQIFILFIFTFFAMLALV LHQKRKRLFLDSNGLFLFSSFALTLLLVALWVAWLWNDPVLRKKYPGVI YVPEPWAFYTLHVSSRHDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for CLN6 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

CLN6-DNA

(SEQ ID NO: 77) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC AATAATGACGTATGTTCCCATAGTAACGCCAATAG GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA TCATATGCCAAGTACGCCCCCTATTGACGTCAATG ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT CTACGTATTAGTCATCGCTATTACCATG AAAGGCAGATGTGTTTGTATTTAAGAGATTGGAGG ATTAAATGAGCTAGAGAGGCTCCCTCCACACGGCC TCATCCTCTGATGGCTGGAAGCCCACCTCTGAGTG TTATTAAATCGATGATGACATCATGGGCACTGCAT GCCCCTCCCTCTGGAGCCCAGCAGGCTTGCAAAGC CTGCAGAGGATAAGAAATTGGGGTCAGAGCGGGAA GCCTCAATCCTTCTTCTCTGGTGTATACCGAGATC GATGTGTAGATCAGATTCACCAGAATTAAATCTGG GGCCCCGTCTGAGTGCTGTCCTTGGCTGACCCTTG GGCACAGTACTTCAGCTCAGGGCCTAGGTTTTTCT CTGCTACAAAACAGAGACAATCACCTGTTCTCCTT ACGACCTGGTGTGTGTGGATCAAATGAAACAAGGA AAGCTTTAAAGCAAATGTGTTCTTCAGGGGACCAG GGGCGGAGGGGGGGGATTGAGGTGTGGCCTGTGGG CTGCTAGAGCCCAGGATGGGGCTGATGGAAAATGA CTCCCAGGCAGGCAGTCCTAGCCTCCCACAGCCAA GAAAGGACATGCAGGTTCTGACCAAAGGGGAAAGA AATAAATCCAATAAACATCTCCCAAGAAGAAAGAC AGGAAAGAAAATAGAATGGAAATAGGCATAGCTCA GACCCCTCATGGTCTGGGAAGCAGACCAAGGATAC TGGGCAGGGGAATGGCACATTGCATTTGCATCTGA GGCACATCCCTTCCAAGAGGCACATCCCTTCTGCA GCGGCTTGAGGGCTGGGTGAGAGGAGACAGGACTG GAGACCTGCACATGTCGTGTGCGCCTGGTGTAGCA CGGGGGTGGTGGGGAGAATGGGAGTTGGTTGCAGT TGTTCTAGTTAGCGGCCTGGGCTGCTGACAGTGAC CGTGGGGAGGAGAGAGTTTGTGACATTGACAGTGG TGTGGAAGGTAACCTTTCTGTGGAGGGAAACCTCA GGTCTCGAGACGGGCTATTGTAAATAACTTAGTCC ACCAGTGCTGGGCTCTCTGCTAAGAGTTTCATATA GTCATCACAACTCCAATGTAGTAGATGCAATAGGC ATCTTCTTGTTACAGATGAGTAAACTGAAGCTGTG AGGGGTTGAGCCATTTGCCCGCATCACAGCTAGTT CAAAGTGGTACCACTAATGAAGTCCTGGCAATCTG CCCTGCAGGCTGTTCTCAGGTTTGACCTTTGGTTC TGTTTTTCACTTGAGGATGCTGTCCCCTTAGGTTC TGTCTGTCTTGTATGCTCCGGTGACTCACGAGCCT GTCCACTGGGTTCCCAGGTCTCGCCTCAGCTTCAG ACCACCGGTCCAACAGCCTTCCTGACCCACCTCAA GCTTAATGCGTTCAAAGATGAATCTTTATTTACAC GAAATCTGCTCTAGCCCACTTCCCGGGGGGTGCCT CCACTATCCACCCAGGGGCAGAATCCGGCCACTGC CTGAACTCTTCTCCCCTCACCCCCCACATCCAGAG TCCCAGTCACCATACCTCTCACACGACTCTAGATG TCACCAACTCGCTCCTTCCCACTGTCACCGCCAGC CCCTCACTAGAACATCTGCAACCCACGTGCTGCAC CACGCGGGTGCTACACGTGCAGGTCTCCAGTCCTG CCTCCTCTCCTCCACCCGTAAGAACAAGGGAAATC CCACAGAACCCTCTGCCCCGGGGAGCATTTAAATC AGCTTAGTCTATCTCCAGGTCGCTACCCCGCCCCA GCCCAACACCCAGGCCTCAGTCACCCTAGACAGAG ATTCCCGTACCCAGGCAGGCAAGGGACCCTAACAC ATCCCAGCCCGCTGGTGGTCACGCGCGCAGCCCGG ACAGGCCAGCAGCCCCCGCCCCGCGAGGACGCCAC ACTCGCAGCGCCCGGCCCTCCCCTAGCGGAGCCCG CCCCGTCTCCCTCCGCCCCGCCTCCCTCCGCTCCG CTCCGCTCCGCTCCGCCCCGCCCCGGGTCCGCAGC CCCG

ATGGAAGCCACTAGAAGAAGACAACACTTGGGAGC GACAGGTGGACCCGGTGCGCAGTTGGGAGCCTCCT TTCTTCAAGCTAGGCATGGTAGCGTAAGTGCTGAC GAAGCCGCACGCACTGCACCTTTCCACTTGGATTT GTGGTTTTATTTCACCCTCCAGAATTGGGTTCTGG ATTTCGGGCGACCCATCGCAATGCTGGTGTTCCCG CTTGAGTGGTTCCCCCTTAATAAACCCAGCGTGGG AGACTATTTTCACATGGCATACAACGTGATAACCC CTTTCTTGCTCCTTAAACTCATAGAGCGCAGCCCC AGAACGCTTCCCAGAAGCATAACGTATGTGTCCAT TATTATCTTCATAATGGGTGCCTCAATACACCTTG TCGGAGATAGCGTAAATCACCGACTCCTCTTTTCA GGATACCAACACCACCTGAGTGTTAGGGAAAACCC GATTATTAAGAACCTCAAACCTGAGACCCTTATTG ATTCTTTCGAGCTGCTGTACTATTACGACGAATAC TTGGGTCATTGTATGTGGTATATTCCATTCTTTCT CATTCTCTTCATGTATTTTTCTGGGTGCTTTACGG CAAGCAAGGCGGAGAGCCTTATCCCAGGCCCCGCG CTCCTTCTTGTTGCCCCAAGCGGTCTCTATTATTG GTATCTGGTAACCGAGGGGCAAATATTTATACTTT TTATTTTCACCTTCTTTGCCATGCTCGCCTTGGTT TTGCACCAGAAGAGGAAGAGATTGTTCCTCGATAG CAACGGACTTTTTCTGTTCTCTTCCTTCGCGCTTA CCCTTCTCTTGGTAGCCTTGTGGGTCGCCTGGCTG TGGAATGACCCAGTTTTGCGGAAAAAGTATCCCGG TGTGATCTACGTGCCTGAACCTTGGGCATTCTACA CTCTTCATGTGTCCTCTAGACACGATTATAAGGAT GATGATGACAAATA

The CLN8 protein sequence is:

(SEQ ID NO: 78) MNPASDGGTSESIFDLDYASWGIRSTLMVAGFVFYLGVFVVCHQLSSSLN ATYRSLVAREKVFWDLAATRAVFGVQSTAAGLWALLGDPVLHADKARGQQ NWCWFHITTATGFFCFENVAVHLSNLIFRTFDLFLVIHHLFAFLGFLGCL VNLQAGHYLAMTTLLLEMSTPFTCVSWMLLKAGWSESLFWKLNQWLMIHM FHCRMVLTYHMWWVCFWHWDGLVSSLYLPHLTLFLVGLALLTLIINPYWT HKKTQQLLNPVDWNFAQPEAKSRPEGNGQLLRKKRPDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for CLN8 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

CLN8-DNA

(SEQ ID NO: 79) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC AATAATGACGTATGTTCCCATAGTAACGCCAATAG GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA TCATATGCCAAGTACGCCCCCTATTGACGTCAATG ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT CTACGTATTAGTCATCGCTATTACCATG TGAAATCGTATGGATCAAAGCTGTCCTCTTGGCCT GAGCCGGTTGCTGAGTGCGGGCCACAAGATCAGAT GAGCCAGTTTATCCATCTGGATGGTCCCAGCTAAT TCAGCAAGTGCAAGGTCTGCAAAATATCTCAAGCA CTGTTGTTAGGTTTTTCAATAGTGATGTTATCCCC AGGAGCAATTTAGGGAGGGTCAGAATCTTGTAATC TCCAGCTGCATGAATTCTAAACCATAATTTCTAAT CTTGTGGCTAATTTGTTAGTCCTACAAAGGCAGTC TAGTCTCCAGACAAGAAAAGGATTTGTTTCGGGAA ACCATAAACTAAGTTTCTTCCAAAGTTAGTTTGGC CTACACCCAGGAATGAACAAGGACAGTTTGGAGGT TAAAAGTAGGATGGAGTTGGTTAGGTCAGATCTCT CACTGTCTCAGTTATAATTTTGCAATGGTGGTTTC ACTGGTTTTAAGATGGAGTTTATTTTATTTTATTT TTATTTTTTTGAGACAGAGTTTCATTCTTGTTGCC CAGGCTAGAGTGCCATGGCGTGATCTCAGCTCACT GCAACCTCTGCCTCCTGGGTTCAAGCAATTCTGCT TCAGCCTCCTGAGTAGCTGAGATTACAGGTGCCCA CCACCACACCCGGCTAATTTTTTTCTCCCAAACTG CTGGGATTACAGGCTTGAGCCACCGCGCCCGCCAA GATGGGTTGTTGATTTTAAAACGATGTCACCCTGG CTCTCCTAGGTTCCTGTTCCCCTAACATCATGAAG GCTGCTGGCAGTTCTCTGGCCTCCAGGGAGGCCTC CACACACATTTACCCATGTTCTTAGACAATCCTAG GGACTCAAGGCTTCAACAAACCTAAATGAGCCAGC AGAAAAATAAACTTGAACATGAATGTCAACGTTTT CCCACATGTACTAAAGGGTTATAATAATTTTGAAA TGTTTATTTCAAAGAGCGTTGGTAATTTAAACGTC CTATTTAATCCCCAAAACAGTCCTGAGGGGGAGAT AAGGCAGTTATCTTCATAGTACAGGAAAGGAAAAA AGCGAGGGTCCAAGGCCGACTATACCCTCAGCTCC ATTAGCCCCCGAGGCCTCCCTGACAGGCGGGGCGG ACAATCCCAGTGCAGATGCTCTGTATCGATCGCAT GCTATCGGTTCTTTCAAGGAACGTGTATTGATCAT CAATTAAGTGGTGAGTACTCCTCTAGATGTCGATT CTAAAGAGGGAACAAAACACATTAGACAGAAGAAA CATAAGTAACTCGAATAACAACCTTAGAGAGAAGA AACATAAGTAACTCGAATAACAACCTTAGCAAACT GCGGAAACTCCTACAGACAAAAACTCAGGTGTGGG CGCAGAAGGGCCGGGGATGCGCTCGGTCAAGACTT GAAGGTCCGGGGCTTGGGCCCTGTGTCCTCACCGA GCCCCGGGGAGGCTCCGGCTCCGTCCACACCCGGA GCGCGACTCAGCCGCGGCCGGGGCTCTTCTGGAGA ACGGCGCGGTCAGGCTCTGCCGCAGCTTTCAGGTC CCCTCGGCCCCGTCCGGGTGCAGCGCAACCAGGCT GCCCGCGGAGCCCCACCGCCCCCATGCCGCCGCCC GCCATGGTTCAGCCCGGCCCCGCCCCTCCCGCCGG CCGTGGTTCAGCGCGTCCACCCCGCCGCCCCACAG CGCCCGCCGCGCCGCGCCCCGCCCCCCGCCGCGCC CCGCCCCCCGCCGCGCCCCGCCCCCCGCCGCGCCC CGCCCCCCGCCGCGCCCCGCCCCCCGCCGCGCCCC GCCCCCCGCCGCGCCCCGCCCCCCGCCGCGCCCCG CCCCCCGCCGCGCCCCGCCCCCCGCCGCGCCCCGC CCCCCGCCGCGCCCCGCCCCCCGCCGCGCCCCGCC CCCCGCCGCGCCCCGCCCCCCGCGCCGCGCCCCGC CCCCCGCCGCGCCCCTCCCGCGCCCGCCGCCCCGC CCCTCCCGCGCCCGCCGCCGTCGTAGCGCCTAGGC GGGGCCTCTCGTAGCGACGCCCCCAGGGGGGCAGA ACGCGTGCGCACGCGCGTGCGAACGCGCGTGCGCG GGCGGTGTTTGAGGCCGGC

ATGAATCCCGCGAGTGATGGCGGCACTTCAGAGAG TATCTTTGACTTGGACTATGCATCATGGGGGATAC GCTCAACTCTTATGGTTGCAGGGTTCGTATTTTAT CTGGGGGTTTTTGTTGTCTGTCACCAACTTTCCAG CAGTCTCAACGCCACTTATAGATCCCTTGTGGCTA GGGAGAAAGTCTTTTGGGACTTGGCCGCAACCCGA GCCGTTTTTGGTGTCCAGTCCACGGCGGCTGGACT GTGGGCCCTCCTTGGTGATCCTGTTCTGCACGCTG ATAAAGCCAGAGGCCAACAGAACTGGTGTTGGTTC CATATAACTACGGCGACTGGCTTCTTTTGTTTTGA AAACGTAGCCGTACACCTGTCCAATTTGATCTTCA GAACATTCGACCTCTTTCTGGTAATCCACCATCTT TTCGCCTTTCTCGGCTTTCTTGGATGTCTTGTCAA TCTCCAAGCCGGTCACTACCTCGCAATGACTACTT TGTTGCTCGAAATGTCAACCCCATTTACTTGCGTA TCATGGATGCTGCTGAAAGCGGGATGGAGTGAATC ACTTTTTTGGAAGTTGAATCAGTGGTTGATGATTC ATATGTTTCACTGTCGAATGGTACTGACATATCAT ATGTGGTGGGTCTGTTTCTGGCACTGGGACGGGCT GGTATCTTCACTTTATCTCCCTCACCTGACCCTTT TCCTCGTAGGCTTGGCGCTGCTCACACTGATCATT AATCCTTACTGGACCCACAAGAAAACGCAGCAACT GCTGAACCCTGTGGATTGGAACTTCGCACAGCCCG AGGCCAAGTCACGGCCTGAAGGCAACGGTCAACTG TTGAGGAAGAAGAGACCGGACTATAAGGATGATGA CGACAAATA

The GM2A protein sequence is:

(SEQ ID NO: 80) MQSLMQAPLLIALGLLLAAPAQAHLKKPSQLSSFSWDNCDEGKDPAVIRS LTLEPDPIIVPGNVTLSVMGSTSVPLSSPLKVDLVLEKEVAGLWIKIPCT DYIGSCTFEHFCDVLDMLIPTGEPCPEPLRTYGLPCHCPFKEGTYSLPKS EFVVPDLELPSWLTTGNYRIESVLSSSGKRLGCIKIAASLKGIDYKDDDD K

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for GM2A and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

GM2A-DNA

(SEQ ID NO: 81) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC AATAATGACGTATGTTCCCATAGTAACGCCAATAG GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA TCATATGCCAAGTACGCCCCCTATTGACGTCAATG ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT CTACGTATTAGTCATCGCTATTACCATG CCCAGATACAGAATCTTCTTGGGTCCAAATACCCC CTAGAGGTTTCCCATTGGCCACTTGGTGCTCACCT CATGTAAATGAAGTGGTGGCCCGCAATCAGTCTGA CTGGTTAATCAGAGGCCGAAGTGAAGTTACAAAGG TCATGCTCCTGTGCAAACATCTGATTGGTTGTGGA AAGCAACCAATCAGGCTGAAGTGAAGTTACAAAGT TGCACTTCTATGCAATTTTAACATATAAACTGAAA TGTAGCATAGAAATCGAAATGTACTTTCAATTTCC CATCTGCTGCACAGAAAAGGTGGGGGGTTGTAAAG AGAGTAGCCTCTGGTCCTCTTGTTACTTAGGTGTG GAAAGTTAGGGTTTTCCTTTCGATTTAGTTCTAGG AAGTCAGCGTGAAATGGCCTTAGGTTCCCTGCCTG CAGACTCTATTCTCCTACCTCAGTTGGGCTAGGTG AAAGGGAAGAGTTGATCAGAATGGGAGGATCATTA TGTAAAGTATGGAGCTTAGTTAATAATAGTGTACC AATGTCATGCCCTCAGATTTAAAAAAAATTTTTTA ATTTTTTATTCTTTTGCCACCTCCTTGTCGCTGGC AGTGCCCCCCAGTTATGCACAAGCACAAGCTCTGG GTCTGCAGTCTGAACCCCCGGCCAGGCCACGGGTG TCTTATCAACAATAGAGGAAACGAACAGAACTTTG TAGTATTTTTGCAACTTTTCTGTAAACCAAAATAA AAAGTTTACTTTAAAAAAGATGATCAGGTGAGTTT TAAATTCTACACATGCATTCATGTACTCAACAGAT TGTCTATTATGCATCAGGCACTGGGTATAAATGAG TGCCTGCATCATGATGCCACCCCTTGTGTAGTTTA CAATCCTGTGGTAAATTGGCGGTATTGGTAACAAC ATCCCTGTTTTTTCTAAAAGCAAATCTCCAACTAG TATATTAACCTGACAAAATCTTGGCTGATGGGGTG TCTAAAAAGAAGTCTTGCTCTATTCCTTCCTAGCT GTGCGACCTTGGCAGAGCTAACCTCACTGTGTATC AGTTTCCTCAGTGCTAAAATTGGGGAAGAAAAAAA AAAAGCATTCCCTTGTGCGTCCTTAGCATGCTTTC AAGCAGTTACTAAATGTTAGTTTTTATAACGGTTA TAATTATTAAAAAGATACGGATTCGTGAAGTCAAG AGATCAAGACCGTCCTGGACAACACGGTGAAACCC CGTTTCTACTAAAAACACAAAAATTAGCTGGGCGT GTGGCGCGTGCCTGTAGTCCCAGCTAGTCGAGAGG CTGAGGCGGAAGAATCGCTTGAACCTGGGAGGCAG AGGTTGCAGTGAGCCGAGATCGCGCCACTGCACTC CAGCTCGGGCGACAGAGCGAGAGTCCGTCTCAAAG CAAAAAAAAAAAAAAAAAAGACACACATATGGGGA AGCGTAACATGGCAGAGAGTCTGACATTTTTGTCC GGAAGGACTTGGGGATGAAAACACTGAATCCGCGG TTTCCCAAAGGTCCTTCCAAAGGTGACGGCCCCGG CACGAGTTCACAAACCACAGCTCCGCCCCATCCCC TGCCCGGCCCCGCCCTTCCCAGGAGCTCTGCTCCG CCCCGCCCCCGACTCCGCTCGGCCCCTCCTCGCGC CACGCCCCCGCCCCTCCCGCGCGCGCAGCTCCGCC CCGCCCTCGTGATCCCGCCCCAACCTCGTGCTAAG CTCCCTTCCGTTCCAGCCGCCTTCAGCCCCGCCGC GCTCAGTTCCGCCCCTTTCTCTTCCAACTCCGCCT ACGCCCCAGAGAGGGAAGGCCTTGACACCTACGCT AGAGAGACAGGCTCCAATGAAAAGAGCGAGGGGGC GGAGCCGGGAGGAATCGGTCCAATTCTCGGCCGGG AAGTCTCTGGCCGGGACGGGGCAGGGCGAACCTGC CAGTGACTGGACTCAGCTTCTTTGCGTAACCAATA CTGGAAGGCATTTAAAGGCACCTCTGCCGCCACAG ACCT

ATGCAGTCTCTCATGCAAGCTCCTCTCTTGATCGC CCTTGGTCTGCTTTTGGCTGCCCCAGCACAAGCTC ACCTGAAAAAACCTTCCCAACTTAGCTCCTTTTCC TGGGATAATTGCGATGAAGGAAAGGACCCGGCTGT AATCCGAAGTTTGACACTCGAACCTGACCCCATCA TCGTCCCGGGCAATGTCACGCTTTCAGTAATGGGT AGCACGAGCGTTCCGCTCTCTAGCCCATTGAAAGT AGACCTCGTGTTGGAAAAAGAAGTAGCCGGGTTGT GGATAAAAATTCCATGCACGGATTATATTGGCTCA TGTACCTTTGAACACTTTTGCGATGTTTTGGACAT GTTGATCCCCACAGGCGAGCCATGTCCAGAGCCCC TTAGGACGTATGGGCTTCCGTGTCACTGCCCATTC AAGGAAGGTACATATAGCCTGCCGAAGTCAGAATT TGTCGTCCCTGATCTCGAATTGCCTAGTTGGCTGA CAACCGGCAACTATCGAATTGAATCTGTACTTTCT TCAAGCGGTAAACGGCTCGGCTGTATCAAAATAGC CGCCTCCCTGAAGGGGATAGACTACAAGGACGACG ACGATAAATA

The HYAL1 protein sequence is:

(SEQ ID NO: 82) MAAHLLPICALFLTLLDMAQGFRGPLLPNRPFTTVWNANTQWCLERHGVD VDVSVFDVVANPGQTFRGPDMTIFYSSQLGTYPYYTPTGEPVFGGLPQNA SLIAHLARTFQDILAAIPAPDFSGLAVIDWEAWRPRWAFNWDTKDIYRQR SRALVQAQHPDWPAPQVEAVAQDQFQGAARAWMAGTLQLGRALRPRGLWG FYGFPDCYNYDFLSPNYTGQCPSGIRAQNDQLGWLWGQSRALYPSIYMPA VLEGTGKSQMYVQHRVAEAFRVAVAAGDPNLPVLPYVQIFYDTTNHFLPL DELEHSLGESAAQGAAGVVLWVSWENTRTKESCQAIKEYMDTTLGPFILN VTSGALLCSQALCSGHGRCVRRTSHPKALLLLNPASFSIQLTPGGGPLSL RGALSLEDQAQMAVEFKCRCYPGWQAPWCERKSMWDYKDDDDK 

The proprietary viral enhancer sequences, native promoter sequences, coding sequence for HYAL1 and the 5′ and 3′ UTR sequences are listed below using the same nomenclature.

HYAL1-DNA

(SEQ ID NO: 83) GCGCAGCACCATGGCCTGAAATAACCTCTGAAAGA GGAACTTGGTTAGGTACCTTCTGAGGCGGAAAGAA CCAGCGTTACATAACTTACGGTAAATGGCCCGCCT GGCTGACCGCCCAACGACCCCCGCCCATTGACGTC AATAATGACGTATGTTCCCATAGTAACGCCAATAG GGACTTTCCATTGACGTCAATGGGTGGAGTATTTA CGGTAAACTGCCCACTTGGCAGTACATCAAGTGTA TCATATGCCAAGTACGCCCCCTATTGACGTCAATG ACGGTAAATGGCCCGCCTGGCATTATGCCCAGTAC ATGACCTTATGGGACTTTCCTACTTGGCAGTACAT CTACGTATTAGTCATCGCTATTACCATG GGACTTGCTGGTGACACAGCCTCAGGAAGTCCTGA GGACATGTGCCCAGGGCGGTTGGGGCACAGCTTGG TTTTATAGATTTTAGGGAGACATGAGACATTAATC AATATGTAAGAAGTACATTAGTTCCAGAAAGAAAG GTGGAGACTGCTCAAATCAAGGCTCCCAGGCTCAA AGCACTGGGGGCTTCCAGGTCACAGATAGGTGAGA GACAGATGGTTGCATTCTTTTGAGTTTCTGGTAAG TCTTTCCAAAGGAGGCAATCAGAATATGCATCTAT CTCTGTGAGCAAAAGGATGACTTGAATAGAATGGG AGGCAGATTTGTCCTGAGCAGTTCCCAGCTTGAAG AGGCCCAAGATACTTTCCTTTCACATTTACCCCAT TTTCTTTTTCAAAATCTTTTGGAGAAAGCATTTTG CAAGAAAATGAGTATCTGGTCTCAGGTTTCATCTG ATCTCTCATTGCTAGATAAGTAGGTCCGGAAAGCT CATTTTTAGCAGGTTGTAAAGTCTCATGCAGTGTG AAGAGAAAATAGGGAGAAGGAAGGAAGAGAAAAAA AAAACAGCAAAAGAACAATCCCAGCCCTGGCGGGG TGGCTCATGCCTGTAATCCCAACAATTTGGGAGGC TGAGGCGGGTGGATCACCTGCGGTTGGGAGTTCGA GAACAGCCTGACCAACATGGAGAAACTCTGTCTCT ACTGAAAATACAAAAAACTAGCCAGGCATGGTGGC TCATGCCTGTAATCCCAGCTACTCAGGAGGCTGAG ACAGGAGAATCACTTGAACCCAGGAGGCGGAGGTT GCAGCAACCTGACATTGCGCCATTGCACTCCAGCC TGGGCAACAAGAGTGAAACTCCATCTCAAAAAAAA AAAAAAAAAAAATCCTGGGAAAATATAGGCCACAT TACTCTGAAGTCCATACATTGGTAGGCAGGTATGA AAGTGGCTTATGTATGTACATAAACAGGTTACTGT TACTTTCTTCTGAAGTGTAAGTTGTCTGACTTTAG TTGACACGCTTTTAAGAAACCACAGCTAGGGCCGG GCGCAGTGACTAACGCCTGTAATCCCAGCACTTCG AAGAGGCCGAGGCGGCCGGATCACAAGGTCAGGGT TCGAGACCAGCCTGGTCAATATGGTGAAACCCTGT CTCTACTAAAAATACAAAAATTAGCCAGGCATGGT AGCAAGCGCCTGTAGTCCCAGCTACTCGGGAGGCT GAGGCAGGAGAATTGCTTGAACCTGGGAGGCATAA GTTGCAGTGAGCTGAGATCGCGCCACTGCACTCCA GCCTGGGTGACAGAGCGAGACTCCATCTCAAAAAA AAAAAAAAAAGAAACCACAGTGGCCGATTGCAGTG GCTCCCCCTCCCCCTCCCCCTCCCCTCCCCCTCCC CCTCCCCCTCTCCCTCCACGGTCTCCCTCTGATGC CGAGCGGAAGCTGGACTGTACTGCTGCCATCTCGG CTCACTGCAACCTCCCTGCCTGATTCTCCTGCCTC AGCCTGCCGAGTGCCTGCGATTGCAGGCACGCGCC GCCACGCCTGACTGGTTTTCGTATTTTTTGGGTGG AGACGGGGTTTCGCTGTGTTGGCCGGGCTGGTCTC CAGCTCCTAACCGTGAGTGATCTGCCAGCCTCGGC CTCCCGAGGTGCTGGGATTGCAGACGGAGTCTCTC AATGGTGCCCAGGCTGGAGTGCAGTGGCGTGATCT CGGCTCGCTACAACATCCACCTCCCAGCAGCCTGC CTTGGCCTCCCAAAGTGCCGAGATTGCAGCCTCTG CCCGGCCGCCACCCCGTCTGGGAAGTGAGGAGCGT CTCTGCCTGGCCGCCCATCGTCTGGGATGTGAGGA GCCCCTCTGCCTGGCTGCCCAGTCTGGAAAGTGAG GAGCGTCTCTGCCCAGCCGCCATCCCATCTAGGAA GTGAGCAGCGCCTCTTCCCGGCCGCCATCCCATCT AGGAAGTGCGGAGCCTCTCTGCCCGGCCACCCATC GTCT

ATGGCAGCGCATCTCCTCCCGATATGTGCACTTTT TCTGACTCTTCTTGATATGGCACAAGGATTTCGGG GTCCGCTCTTGCCTAATCGACCTTTTACAACAGTA TGGAATGCTAACACACAGTGGTGCCTTGAAAGGCA CGGTGTCGACGTTGACGTCTCCGTCTTCGACGTAG TAGCCAATCCAGGCCAAACCTTCAGGGGGCCAGAT CATGACTATCTTCTATAGTTCTCAACTGGGGACTA TCCCTACTACACCCCCACGGGTGAACCTGTATTCG GCGGGTTGCCACAGAATGCTAGCCTTATCGCGCAC CTGGCCAGGACGTTTCAAGACATACTCGCCGCCAT TCCAGCACCCGACTTCTCTGGTCTGGCTGTGATCG ATTGGGAGGCCTGGCGACCTAGGTGGGCTTTCAAC TGGGATACCAAGGACATCTATAGGCAGCGGAGCCG AGCATTGGTGCAAGCCCAGCATCCGGATTGGCCAG CGCCTCAGGTGGAAGCGGTAGCGCAGGATCAATTC CAGGGCGCCGCGAGAGCTTGGATGGCCGGGACATT GCAACTTGGGAGAGCCTTGAGGCCTCGCGGCCTGT GGGGTTTTTATGGATTCCCAGATTGCTACAACTAT GATTTTCTCTCTCCAAATTACACAGGCCAATGTCC AAGCGGCATACGCGCACAGAACGATCAGCTTGGCT GGCTCTGGGGACAATCTCGAGCCTTGTACCCTAGC ATCTATATGCCAGCTGTCTTGGAGGGCACCGGAAA ATCTCAGATGTACGTGCAACATAGGGTTGCAGAGG CCTTCCGGGTTGCCGTCGCAGCCGGAGATCCGAAT CTGCCTGTTCTTCCCTATGTACAGATCTTTTATGA TACCACAAATCACTTTTTGCCGTTGGACGAGCTTG AACATAGTTTGGGTGAAAGTGCGGCCCAAGGTGCG GCGGGAGTAGTTCTTTGGGTTTCCTGGGAAAATAC ACGGACTAAAGAGTCATGTCAGGCCATAAAGGAGT ACATGGATACCACACTGGGCCCTTTCATTTTGAAT GTTACGAGTGGCGCGTTGCTTTGTAGTCAGGCACT GTGCAGCGGACACGGCAGGTGTGTGCGGCGGACGT CACATCCAAAGGCCCTGCTGCTGCTGAACCCGGCG TCATTTTCAATTCAACTTACTCCCGGTGGGGGGCC CCTCTCACTTAGGGGCGCGCTCTCCCTGGAAGACC AGGCCCAGATGGCAGTAGAGTTTAAGTGCAGATGT TACCCAGGGTGGCAGGCGCCTTGGTGCGAGCGCAA ATCCATGTGGGATTACAAAGATGATGATGATAAGT A

In certain embodiment, any of the GOI described herein are codon optimized for manufacturing, optimal expression in a host cell, such as in a human cell. Further Codon optimization of GOI can be done based on codon optimization table publically available, such as the Codon and Codon Pair Usage Tables (CoCoPUTs) maintained at the George Washington University (GWU). The CoCoPUTs is derived from all available GenBank and RefSeq data source.

In certain embodiment, the GOI's are codon optimized for expression in neuronal tissues or specific cell types in neuronal tissues, such as neurons, depending on the target cell type the GOI's are to be expressed. This can be done using TissueCoCoPUTs, which are human tissue-specific codon and codon pair usage tables derived from human genomic codon usage information and tissue-specific transcriptomic data. The TissueCoCoPUTs maintained by the GWU website represent 52 human tissues. Transcriptomic data are derived from the Genotype Tissue Expression (GTEx) Portal.

3. Delivery Methods

In certain embodiments, the viral vectors (such as AAV) of the invention are delivered to neuronal target cells by intravenous injection or direct intraparenchymal injection or direct intracranial injection. Such delivery means effectively bypass the BBB, and are common means for the administration of gene therapeutics to the brain. In certain embodiments, the neuronal target cells intended to receive gene therapy through intraparenchymal injection are clustered in a focal location, and are this particularly suitable for focal delivery of the viral vector.

In certain embodiments, the viral vector (such as AAV) of the invention is delivered locally or compartmentally, such as direct intraocular injection, or injection in the cochlea.

In certain embodiments, the viral vectors of the invention are delivered to neuronal target cells by intravenous injection.

In certain embodiments, the neuronal target cells intended to receive gene therapy through intravenous injection are globally located in the CNS, or in multiple CNS regions. Such global delivery across the BBB is achieved by using selected AAV serotypes (such as AAV9) that have been shown to deliver genes across the BBB after intravenous injection.

In certain embodiments, the viral vector (such as AAV) of the invention is delivered to achieve widespread delivery for diseases of extensive pathology including glioblastoma multiforme (GBM), lysosomal storage diseases (LSDs), Alzheimer's disease, Parkinson's disease and Canavan's disease. In certain embodiments, the viral vectors are delivered intracerebroventricularly, intrathecally, intranasally, or systemicaly (e.g., intravenous and intra-arterial injections).

The systemic delivery route for gene delivery vehicles is very promising, and has the potential to be a conduit to the entire CNS (every cell in the brain is a maximum distance of 40 μm from an endothelial cell), provided that the issue of BBB blockage and the filtration systems of the spleen and liver are adequately dealt with.

In certain embodiments, the viral vectors (such as AAV) of the invention are delivered to neuronal target cells by intravascular, intrathecal, and/or cerebrospinal fluid (CSF) administration. Many AAV capsids, such as AAV9, AAV2.5, rAAVrh.39, rAAVrh.43, rAAV7, rAAVrh.8 and rAAVrh.10, have remarkable CNS tropism after vascular (Foust et al., Nat Biotechnol. 27:59-65, 2009; Gray et al., Gene Ther. 20:450-459, 2013; Zhang et al., Mol Ther. 19:1440-1448, 2011; Bevan et al., Mol Ther. 19:1971-1980, 2011; Yang et al., Mol Ther. 22:1299-1309, 2014; Duque et al., Mol Ther. 17:1187-1196, 2009), and CSF administration (Samaranch et al., Hum Gene Ther. 24:526-532, 2013; Gray, supra; Samaranch et al., Hum Gene Ther. 23:382-389, 2012).

In certain embodiments, the viral vectors (such as AAV) of the invention are delivered to neuronal target cells by direct intracranial injection. A large range of AAV capsids, including pseudotypes rAAV2/1, rAAV2/2, and rAAV2/5, hu.32, hu.37, pi.2, hu.11, rh.8, hu.48R3, bb2, cy5, rh20, rh39, rh43, AAV7, AAV8, and AAV9, have been demonstrated for their CNS gene transfer properties by direct intracranial injection (Burger et al., Mol Ther. 10:302-317, 2004; Cearley et al., Mol Ther. 16:1710-1718, 2008; Cearley and Wolfe, Mol Ther. 13:528-537, 2006; Lawlor et al., Mol Ther. 17:1692-1702, 2009). Vectors based on distinct AAV serotypes or pseudotypes can be chosen for specific applications in the nervous system, depending on their preferential or global tropism within the different regions of the brain and target neuronal tissues.

In certain embodiments, the viral vector is AAV9. The vast majority (>90%) of cells in the CNS transduced by intravenously injected AAV9 using strong promoters like CBA are astrocytes and neurons. The distribution of vector is widespread with transduced cells detected in all areas of the brain from the olfactory bulb to cerebellum.

In certain embodiments, delivery of the viral vectors of the invention across the BBB is further enhanced by a variety of techniques including: intra-nasal administration and/or intracranial NSC transplantation that bypasses the BBB; transiently permeating the BBB using osmotic manipulation; magnetic resonance imaging guided focused ultrasound (MRIgFUS) to selectively open the BBB and allow therapeutics to pass into the parenchyma; convection enhanced delivery (Debinski and Tatter, Curr Opin Mol Ther. 12:647-653, 2010); introduction into a fluid space, e.g., vasculature, brain ventricles or intrathecal space in the spinal cord, such that cells lining the space produce the deficient protein (Chen et al., Nat Med. 15:1215-1218, 2009); injection into regions of the brain that serve as a nexus of interconnections with retrograde transport of vectors, such as the thalamus, e.g., for AAV (McCurdy et al., Sci Transl Med. 6:231ra48, 2014); and/or by taking advantage of the “bystander effect” whereby proteins released from the producer cells can be taken up by the deficient cells (McCurdy; Chen, Supra).

In certain embodiments, the viral vector (such as AAV) of the invention comprises a targeting peptide that bind selectively to the brain endothelial cells or a brain endothelial cell receptor (such as the low-density lipoprotein (LDL) and other related receptors that can be targeted by Apolipoprotein E-derived peptides) to target the viral vector to the brain vasculature.

4. Viral Production

Another aspect of the invention provides a method of producing the rAAV vector of the invention, comprising introducing the rAAV vector of the invention into a packaging cell line that constitutively or inducibly provides rep/cap proteins in trans.

In certain embodiments, the packaging cell line is a HEK293 cell line, a HeLa cell, or an A549 cell.

In general, the subject rAAV vector can be produced using any of many art-recognized approach. In certain embodiments, the rAAV vector is produced based on the helper-virus-free transient transfection method with all cis and trans components (e.g., vector plasmid and packaging plasmids, along with helper genes isolated from adenovirus) in host cells such as 293 cells. In certain embodiments, the rAAV vector is produced using recombinant herpes simplex virus (rHSV)-based AAV production system, which utilizes rHSV vectors to bring the AAV vector and the Rep and Cap genes into the cells. In certain embodiments, the rAAV vector is produced based on baculovirus system which requires simultaneous infection of insect cells with several baculovirus vectors to deliver the rAAV vector cassette and the Rep and Cap genes. In certain embodiments, the rAAV vector is produced based on the AAV producer cell lines derived from HeLa or A549, which stably harbored AAV Rep/cap genes. The AAV vector cassette can either be stably integrated in the host genome or be introduced by an adenovirus that contained the cassette. 

1. A recombinant adeno-associated viral (rAAV) vector, comprising: (1) a polynucleotide comprising a gene of interest (GOI), under the transcriptional control of the native/endogenous promoter of said GOI; (2) a heterologous enhancer that enhances transcription of the GOI from the native/endogenous promoter; and, (3) a pair of inverted terminal repeat (ITR) flanking the polynucleotide.
 2. The rAAV vector of claim 1, wherein GOI is a neuronal gene, or is a gene expressed in neuronal tissues (CNS and/or PNS).
 3. The rAAV vector of claim 1 or 2, wherein the GOI is defective (e.g., loss-of-function) in a neuronal disease or condition.
 4. The rAAV vector of claim 3, wherein the neuronal disease or condition is a CNS disease or condition.
 5. The rAAV vector of claim 4, wherein the CNS disease or condition is: Ceroid-Lipofuscinosis, Fucosidosis, Giant Axonal Neuropathy, Globoid cell leukodystrophy, Mucolipidiosis Type IV, Neuronal Ceroid Lipofusinoses, Niemann-Pick Disease, Sandhoff Disease, Sanfilippo syndrome, Tay-Sachs Disease, Hunter Syndrome, Sialidosis, Multiple Sulfatase Deficiency, Childhood Epilepsy, CMT Peripheral Neuropathy, Neuronal Ceroid Lipofusinoses, Aspartylglycosaminuria, Mucopolysaccharidoses, Parkinsons Disease/Symptoms, GM1-Gangliosidosis, Charcot-Marie-Tooth Type 1A, Retts Syndrome, Dannon Disease, Mucopolysaccharidoses (due to GNS, HGSNAT, NAGLU, or ARSB), Sly Syndrome, Biotin basal ganglia disease, Pelizaeus-Merzbacher disease, Neuronal Ceroid Lipofusinoses, Canavan Disease, Beta-Mannosidosis, Wolman Disease, Cystinosis, Alzheimer's Disease/Symptom, Salla Disease, Jansky-Bielschowsky disease, Neuronal ceroid lipofuscinoses, or GM2 gangliosidosis.
 6. The rAAV vector of any one of claims 1-5, wherein the GOI is: CLN3, FUCA1, GAN, GALC, MCOLN1, PPT1, SMPD1, HEXB, SGSH, HEXA, IDS, NEU1, SUMF1, GAT1/SLCA1, FIG. 4 , CLNS, AGA, IDUA, GDNF, GLB1, PMP22/MFN2, MECP2, LAMP2, NAGLU, ARSB, GUSB, SLC19A3, PLP1, TPP1/CLN2, ACY2/ASPA, MANBA, LIPA, CTNS, GNS, HGSNAT, NEUROD1, SLC17A5, CLN6, CLN8, or GM2A.
 7. The rAAV vector of any one of claims 1-6, wherein the rAAV has a tropism for neuronal cells, or for a cell in neuronal tissue.
 8. The rAAV vector of claim 7, wherein the rAAV is AAV9, AAV2.5, rAAVrh.39, rAAVrh.43, rAAV7, rAAVrh.8 or rAAVrh.10, preferably AAV9.
 9. The rAAV vector of claim 7, wherein the rAAV comprises AAV9, AAV2.5, rAAVrh.39, rAAVrh.43, rAAV7, rAAVrh.8 and rAAVrh.10 capsids, preferably AAV9 capsids.
 10. The rAAV vector of any one of claims 1-9, wherein the polynucleotide further comprises a 5′-UTR coding region, and a 3′-UTR coding region.
 11. The rAAV vector of any one of claims 1-10, wherein the heterologous enhancer is a viral enhancer.
 12. The rAAV vector of claim 11, wherein the viral enhancer is CMV enhancer.
 13. The rAAV vector of claim 11, wherein the viral enhancer is SV-40 enhancer.
 14. The rAAV vector of claim 11, wherein the heterologous enhancer comprises a polynucleotide of SEQ ID NO:
 1. 15. A pharmaceutical composition comprising the rAAV vector of any one of claims 1-14.
 16. The pharmaceutical composition of claim 15, which is formulated for intravenous administration (e.g., to the blood) or intrathecal administration (e.g., to spinal fluid).
 17. A cell infected with the rAAV vector of any one of claims 1-14.
 18. A recombinant AAV virus comprising the rAAV vector of any one of claims 1-14, wherein the serotype or pseudotype of the recombinant AAV virus is for preferential infection of a neuronal cell or a cell in neuronal tissue.
 19. A method of treating a (genetic) disease or disorder in a subject, the method comprising administering the recombinant AAV virus of claim 18 into the subject.
 20. The method of claim 19, wherein the genetic disease or disorder is a neuronal disease or disorder, and/or wherein the recombinant AAV virus preferentially infects a neuronal cell or a cell in neuronal tissue of the subject, thereby treating the neuronal disease or disorder.
 21. The method of claim 19 or 20, wherein the rAAV virus is administered to the subject intravenously or intrathecally.
 22. A method of producing the rAAV vector of any one of claims 1-14, comprising introducing the rAAV vector of any one of claims 1-14 into a packaging cell line that constitutively or inducibly provides rep/cap proteins in trans.
 23. The method of claim 22, wherein said rep/cap proteins comprise one or more AAV9 capsid proteins. 